Chinese Doctors Use 3D-Printing in Pioneering Surgery to Replace Half of Man’s Skull
Surgeons at Xijing Hospital in Xi’an, Shaanxi province in Northwest China are using 3D-printing in a pioneering surgery to help rebuild the skull of a man who suffered brain damage in a construction accident.
Hu, a 46-year-old farmer, was overseeing construction to expand his home in Zhouzhi county last October when he was hit by a pile of wood and fell down three storeys.
Although he survived the fall, the left side of his skull was severely crushed and the shattered bone fragments needed to be removed, which has led to a depression of one side of his head.
Due to his injuries, Hu cannot see well out of his left eye, experiences double vision (diplopia) and is also unable to speak and write.
While reading, children and adults alike must avoid confusing mirror-image letters (like b/d or p/q). Why is it difficult to differentiate these letters? When learning to read, our brain must be able to inhibit the mirror-generalization process, a mechanism that facilitates the recognition of identical objects regardless of their orientation, but also prevents the brain from differentiating letters that are different but symmetrical. A study conducted by the researchers of the Laboratoire de Psychologie du Développement et de l’Education de l’Enfant (CNRS / Université Paris Descartes / Université de Caen Basse-Normandie) is available on the website of the Psychonomic Bulletin & Review (Online First Articles).
In recent years, many studies on the process of learning to read have been based on the neuronal recycling hypothesis: the reuse of old brain mechanisms in a new adaptive role —a kind of “biological trick.” Specifically, neurons that are originally dedicated to the rapid identification of objects in the environment, through the mirror-generalization process, are “repurposed” during childhood to specialize in the visual recognition of letters and words.
In this study, the researchers showed 80 young adults pairs of images, first two letters and then two animals, asking them to determine whether they were identical. The readers consistently spent more time determining that two animal images, when preceded by mirror-image letters, were indeed identical. This increase in response time is called “negative priming”: the readers had to inhibit the mirror-generalization process in order to distinguish letters like b/d or p/q. They then needed a little more time to reactivate this strategy when it became useful again to quickly identify animals.
These results show that even adults need to inhibit the mirror-generalization process to avoid reading errors. Children must therefore learn to inhibit this strategy when learning to read. A failure of cognitive inhibition during the recycling of visual neurons in the brain could thus be a factor in dyslexia— a direction worth exploring, in light of these findings.
Memory in silent neurons
When we learn, we associate a sensory experience either with other stimuli or with a certain type of behaviour. The neurons in the cerebral cortex that transmit the information modify the synaptic connections that they have with the other neurons. According to a generally-accepted model of synaptic plasticity, a neuron that communicates with others of the same kind emits an electrical impulse as well as activating its synapses transiently. This electrical pulse, combined with the signal received from other neurons, acts to stimulate the synapses. How is it that some neurons are caught up in the communication interplay even when they are barely connected? This is the crucial chicken-or-egg puzzle of synaptic plasticity that a team led by Anthony Holtmaat, professor in the Department of Basic Neurosciences in the Faculty of Medicine at UNIGE, is aiming to solve. The results of their research into memory in silent neurons can be found in the latest edition of Nature.
Learning and memory are governed by a mechanism of sustainable synaptic strengthening. When we embark on a learning experience, our brain associates a sensory experience either with other stimuli or with a certain form of behaviour. The neurons in the cerebral cortex responsible for ensuring the transmission of the relevant information, then modify the synaptic connections that they have with other neurons. This is the very arrangement that subsequently enables the brain to optimise the way information is processed when it is met again, as well as predicting its consequences.
Neuroscientists typically induce electrical pulses in the neurons artificially in order to perform research on synaptic mechanisms.
The neuroscientists from UNIGE, however, chose a different approach in their attempt to discover what happens naturally in the neurons when they receive sensory stimuli. They observed the cerebral cortices of mice whose whiskers were repeatedly stimulated mechanically without an artificially-induced electrical pulse. The rodents use their whiskers as a sensor for navigating and interacting; they are, therefore, a key element for perception in mice.
An extremely low signal is enough
By observing these natural stimuli, professor Holtmaat’s team was able to demonstrate that sensory stimulus alone can generate long-term synaptic strengthening without the neuron discharging either an induced or natural electrical pulse. As a result – and contrary to what was previously believed – the synapses will be strengthened even when the neurons involved in a stimulus remain silent.In addition, if the sensory stimulation lasts over time, the synapses become so strong that the neuron in turn is activated and becomes fully engaged in the neural network. Once activated, the neuron can then further strengthen the synapses in a forwards and backwards movement. These findings could solve the brain’s “What came first?” mystery, as they make it possible to examine all the synaptic pathways that contribute to memory, rather than focusing on whether it is the synapsis or the neuron that activates the other.
The entire brain is mobilised
A second discovery lay in store for the researchers. During the same experiment, they were also able to establish that the stimuli that were most effective in strengthening the synapses came from secondary, non-cortical brain regions rather than major cortical pathways (which convey actual sensory information). Accordingly, storing information would simply require the co-activation of several synaptic pathways in the neuron, even if the latter remains silent. These findings may also have important implications both for the way we understand learning mechanisms and for therapeutic possibilities, in particular for rehabilitation following a stroke or in neurodegenerative disorders. As professor Holtmaat explains: “It is possible that sensory stimulation, when combined with another activity (motor activity, for example), works better for strengthening synaptic connections”. The professor concludes: “In the context of therapy, you could combine two different stimuli as a way of enhancing the effectiveness.”
How studying damage to the prefrontal lobe has helped unlock the brain’s mysteries
Until the last few decades, the frontal lobes of the brain were shrouded in mystery and erroneously thought of as nonessential for normal function—hence the frequent use of lobotomies in the early 20th century to treat psychiatric disorders. Now a review publishing August 28 in the Cell Press journal Neuron highlights groundbreaking studies of patients with brain damage that reveal how distinct areas of the frontal lobes are critical for a person’s ability to learn, multitask, control their emotions, socialize, and make real-life decisions. The findings have helped experts rehabilitate patients experiencing damage to this region of the brain.
Although fairly common, damage to the prefrontal lobes (also called the prefrontal cortex) is often overlooked and undiagnosed because patients do not manifest obvious deficits. For example, patients with prefrontal brain damage do not lose any of their senses and often have preserved motor and language abilities, but they may manifest social abnormalities or difficulties with high-level planning in everyday life situations.
"In this review, we aimed to highlight a blend of new studies using cutting edge research techniques to investigate brain damage, but also to relate these new studies to original studies, some of which were published more than a century ago," said lead author Dr. Sara Szczepanski, of the University of California, Berkeley. "There is currently a large push to better understand the functions of the prefrontal cortex, and we believe that our review will make an important contribution to this understanding."
In addition to revealing the functions of different areas within the prefrontal cortex, studies have also demonstrated the flexibility of the region, which has helped experts optimize cognitive therapy techniques to enable patients with brain damage to learn new skills and compensate for their impairments.
The review indicates that by studying patients with damage to the prefrontal cortex, investigators can gain insights into this still-mysterious region of the brain that is critical for complex human skills and behavior.
The effects of very early Alzheimer’s disease on the characteristics of writing by a renowned author
Iris Murdoch (I.M.) was among the most celebrated British writers of the post-war era. Her final novel, however, received a less than enthusiastic critical response on its publication in 1995. Not long afterwards, I.M. began to show signs of insidious cognitive decline, and received a diagnosis of Alzheimer’s disease, which was confirmed histologically after her death in 1999. Anecdotal evidence, as well as the natural history of the condition, would suggest that the changes of Alzheimer’s disease were already established in I.M. while she was writing her final work. The end product was unlikely, however, to have been influenced by the compensatory use of dictionaries or thesauri, let alone by later editorial interference. These facts present a unique opportunity to examine the effects of the early stages of Alzheimer’s disease on spontaneous written output from an individual with exceptional expertise in this area. Techniques of automated textual analysis were used to obtain detailed comparisons among three of her novels: her first published work, a work written during the prime of her creative life and the final novel. Whilst there were few disparities at the levels of overall structure and syntax, measures of lexical diversity and the lexical characteristics of these three texts varied markedly and in a consistent fashion. This unique set of findings is discussed in the context of the debate as to whether syntax and semantics decline separately or in parallel in patients with Alzheimer’s disease.
Neural Anatomy of Primary Visual Cortex Limits Visual Working Memory
Despite the immense processing power of the human brain, working memory storage is severely limited, and the neuroanatomical basis of these limitations has remained elusive. Here, we show that the stable storage limits of visual working memory for over 9 s are bound by the precise gray matter volume of primary visual cortex (V1), defined by fMRI retinotopic mapping. Individuals with a bigger V1 tended to have greater visual working memory storage. This relationship was present independently for both surface size and thickness of V1 but absent in V2, V3 and for non-visual working memory measures. Additional whole-brain analyses confirmed the specificity of the relationship to V1. Our findings indicate that the size of primary visual cortex plays a critical role in limiting what we can hold in mind, acting like a gatekeeper in constraining the richness of working mental function.
Effect of Advancing Age on Outcomes of Deep Brain Stimulation for Parkinson Disease
Importance: Deep brain stimulation (DBS) is a well-established modality for the treatment of advanced Parkinson disease (PD). Recent studies have found DBS plus best medical therapy to be superior to best medical therapy alone for patients with PD and early motor complications. Although no specific age cutoff has been defined, most clinical studies have excluded patients older than 75 years of age. We hypothesize that increasing age would be associated with an increased number of postoperative complications.
Objective: To evaluate the stepwise effect of increasing age (in 5-year epochs) on short-term complications following DBS surgery.
Design, Setting, and Participants: A large, retrospective cohort study was performed using the Thomson Reuters MarketScan national database that examined 1757 patients who underwent DBS for PD during the period from 2000 to 2009.
Main Outcomes and Measures: Primary measures examined included hospital length of stay and aggregate and individual complications within 90 days following surgery. Multivariate logistic regression analysis was used to calculate complication-related odds ratios (ORs) for each 5-year age epoch after controlling for covariates.
Results: Overall, 132 of 1757 patients (7.5%) experienced at least 1 complication within 90 days, including wound infections (3.6%), pneumonia (2.3%), hemorrhage or hematoma (1.4%), or pulmonary embolism (0.6%). After adjusting for covariates, we found that increasing age (ranging from <50 to 90 years of age) did not significantly affect overall 90-day complication rates (OR, 1.10 per 5-year increase [95% CI, 0.96-1.25]; P = .17). The 2 most common procedure-related complications, hemorrhage (OR, 0.82 [95% CI, 0.63-1.07]; P = .14) and infection (OR, 1.04 [95% CI, 0.87-1.24]; P = .69), did not significantly increase with age.
Conclusions and Relevance: Older patients with PD (>75 years) who were selected to undergo DBS surgery showed a similar 90-day complication risk (including postoperative hemorrhage or infection) compared with younger counterparts. Our findings suggest that age alone should not be a primary exclusion factor for determining candidacy for DBS. Instead, a clear focus on patients with medication-refractory and difficult to control on-off fluctuations with preserved cognition, regardless of age, may allow for an expansion of the traditional therapeutic window.
New York University biologists have identified a mechanism that helps explain how the diversity of neurons that make up the visual system is generated.
“Our research uncovers a process that dictates both timing and cell survival in order to engender the heterogeneity of neurons used for vision,” explains NYU Biology Professor Claude Desplan, the study’s senior author.
The study’s other co-authors were: Claire Bertet, Xin Li, Ted Erclik, Matthieu Cavey, and Brent Wells—all postdoctoral fellows at NYU.
Their work, which appears in the latest issue of the journal Cell, centers on neurogenesis—the process by which neurons are created.
A central challenge in developmental neurobiology is to understand how progenitors—stem cells that differentiate to form one or more kinds of cells—produce the vast diversity of neurons, glia, and non-neuronal cells found in the adult Central Nervous System (CNS). Temporal patterning is one of the core mechanisms generating this diversity in both invertebrates and vertebrates. This process relies on the sequential expression of transcription factors into progenitors, each specifying the production of a distinct neural cell type.
In the Cell paper, the researchers studied the formation of the visual system of the fruit fly Drosophila. Their findings revealed that this process, which relies on temporal patterning of neural progenitors, is more complex than previously thought.
They demonstrate that in addition to specifying the production of distinct neural cell type over time, temporal factors also determine the survival or death of these cells as well as the mode of division of progenitors. Thus, temporal patterning of neural progenitors generates cell diversity in the adult visual system by specifying the identity, the survival, and the number of each unique neural cell type.
How nerve cells within the brain communicate with each other over long distances has puzzled scientists for decades. The way networks of neurons connect and how individual cells react to incoming pulses in principle makes communication over large distances impossible. Scientists from Germany and France provide now a possible answer how the brain can function nonetheless: by exploiting the powers of resonance.
(Image caption: Resonance in the activity of nerve cells (left) allows activity within the brain to travel over large distances, e.g. from the back of the head to the front during the processing of visual stimuli. Credit: Gunnar Grah/BrainLinks-BrainTools)
As Gerald Hahn, Alejandro F. Bujan and colleagues describe in the journal “PLoS Computational Biology”, the ability of networks of neurons to resonate can amplify oscillations in the activity of nerve cells, allowing signals to travel much farther than in the absence of resonance. The team from the cluster of excellence BrainLinks-BrainTools and the Bernstein Center at the University of Freiburg and the UNIC department of the French Centre national de la recherche scientifique in Gif-sur-Yvette created a computer model of networks of nerve cells and analyzed its properties for signal propagation.
Earlier propositions how information travels through the brain had the flaw of being biologically implausible. They either postulated strong connections between distant brain areas for which there was no evidence, or they required a global mechanism setting these distant parts of the brain into linked oscillations. However, nobody could explain how this could actually be implemented.
The simulation study of Hahn and Bujan required neither unrealistic network properties nor the existence of a pacemaker for the brain. Instead, they found that resonance could be the key to long-distance communication in networks with relatively few and weak connections, as it is the case in the brain. Not all nerve cells excite other cells; some inhibit the activity of others. This means that the activity in a network can oscillate around a certain level of activity as a result of the interplay of excitation and inhibition. These networks typically have preferred frequencies at which oscillations are particularly strong, just as a taut string on a violin has a preferred frequency. If the activity tunes into this frequency, pulses propagate much farther. As the scientists point out, the combination of oscillatory signals together with resonance induced amplification may be the only possible form of long distance communication in certain cases. They further suggest that a network’s ability to change its preferred frequency may play a role in the way how information is at times processed differently in the brain.