connectome A term coined by Olaf Sporns, by analogy with the genome (the map of genes), the connectome is the map – or wiring diagram – of all the connections in the brain. While the broad outlines of the human connectome are known, we are very far from unravelling the connectome in all its detail.
cerebral cortex The deeply folded outer layers of the brain, which take up about two-thirds of its entire volume and are divided into left and right hemispheres that house the majority of the ‘grey matter’ (so called because of the lack of myelination which makes other parts of the brain seem white). The cerebral cortex is separated into lobes, each having different functions, including perception, thought, language, action and other ‘higher’ cognitive processes such as decision making.
default mode network (DMN) A group of brain regions whose activity (typically when measured by fMRI) is reduced during the performance of an externally directed task, and is more active in states of wakeful rest, mind-wandering, introspection or inwardly directed attention. In general, the DMN has been associated with self-related processing. It includes medial parts of the prefrontal and temporal lobes and the posterior cingulate cortex.
diffusion tensor imaging (DTI) DTI is a relatively recent neuroimaging technique that uses magnetic resonance imaging (MRI) to chart the long-range bundles of connections (axons) that course throughout the brain. The method depends on the fact that water molecules diffuse preferentially along axons, instead of across them.
electroencephalography (EEG) The practice of detecting the tiny variations in electrical field at the surface of the brain, which are produced by the activity of populations of neurons in the underlying cortex. EEG has very good resolution in time but is relatively poor (as compared to fMRI) in localizing activity in space. A related method – magnetoencephalography (MEG) – measures the corresponding magnetic field variations. MEG can be more sensitive than EEG but is a much more complex and expensive technology.
frontal lobes One of the four main divisions of the cerebral cortex and the most highly developed in humans as compared with other animals. The frontal lobes (one for each hemisphere) house areas associated with decision making, planning, memory, voluntary action and personality.
(functional) magnetic resonance imaging (f)MRI MRI technology has revolutionized neuroscience by allowing non-invasive mapping of the three-dimensional structure of the brain, taking advantage of the way different parts of the brain react under strong magnetic fields. fMRI extends MRI to measure brain activity and is based on measuring the differences in blood oxygenation that go along with neural activity. fMRI has very good spatial resolution but poor time resolution, as compared to EEG.
neurons The cellular building blocks of the brain. Neurons carry out the brain’s basic operations, taking inputs from other neurons via dendrites, and – depending on the pattern or strength of these inputs – either releasing or not releasing a nerve impulse as an output. Neurons come in different varieties but (almost) all have dendrites, a cell body (soma) and a single axon.
neuropsychology This is the discipline of inferring the function of different brain regions based on the behaviour and reported experiences of patients who have experienced damage to specific regions. For example, the amnesia in patient H.M. following hippocampal damage allowed neuropsychologists to associate the hippocampus with (episodic) memory.
phrenology Popularized by Franz Gall in the 19th century, phrenology is the now discredited practice of inferring personality and mental attributes from the various lumps and bumps on the surface of the skull. Although he was wrong about this, Gall was very much right in the idea that different parts of the brain did different things, thus laying the foundations for neuropsychology and even modern fMRI.
transcranial magnetic stimulation (TMS) A technique in which short but powerful magnetic pulses are applied to the scalp, briefly stimulating the neurons in the underlying cortex. By perturbing brain activity in specific regions and observing what happens, TMS can help determine the function of these regions. Recently, TMS has been combined with EEG so that brain as well as behavioural responses to TMS pulses can be recorded.
Brain mapping started shakily in the late 18th century with the pseudoscience of phrenology, which attributed bumps on the skull to specific psychological traits. Partly to refute phrenology, Paul Broca published a landmark study in 1861, in which he reported on a patient, Leborgne, who understood what was said to him but whose speech had so degraded that he could only ever say one word, ‘tan’. Leborgne had just died and the autopsy carried out by Broca found local damage in a restricted part of the left frontal lobe. Although this was only one patient, it was, crucially, direct evidence to link function with region. Broca went on to find many speech-impaired patients with the same damaged brain area. Later, Carl Wernicke added to this picture by using the same method to link understanding of language with a portion of the left temporal lobes. These cases helped give birth to a new kind of science, that of neuropsychology, in which brain-damaged patients are examined for deficits, enabling us to learn what regions are crucial for a given function. Over the past 150 years, countless brain-damaged patients have helped build up a picture of a brain with many specialist subunits, each playing their part in our thoughts and feelings.
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Science can link function to brain region, via patients unfortunate enough to experience brain damage along with a discrete mental impairment.
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Neuropsychology was always a messy business. For instance, brain damage rarely creates a neat, discrete lesion, while intact regions can sometimes take over a given function from a damaged one. But for many decades, this method was the main brain-mapping tool in town. Now, though, neuropsychology has fallen somewhat out of fashion, with modern brain-scanning techniques, such as fMRI efficiently able to search across the whole brain for links to a specific function in healthy subjects.
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PAUL BROCA
1824–80
Discovered the speech production area
CARL WERNICKE
1848–1905
Discovered the speech comprehension area
ALEXANDER LURIA
1902–77
Father of modern neuropsychology
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Daniel Bor
Phineas Gage and the tamping iron that went right through his brain, leaving him alive but changing his mind.
Just as astronomy and biology were revolutionized by the telescope and microscope, neuroscience has been transformed by brain-imaging technologies. Some scan types, such as magnetic resonance imaging (MRI), non-invasively reveal the three-dimensional structure of the brain. These are useful for exploring how the brain is constructed and how neural anatomy differs among people. They also provide vital clinical tools for detecting various kinds of brain damage. A more recent development is diffusion tensor imaging (DTI), which provides a three-dimensional map of the main wires connecting brain regions together. But what has truly revolutionized neuroscience are technologies that observe the brain’s activity. Electroencephalography (EEG) has played a part in this by revealing the brain’s changing patterns of electrical activity, millisecond by millisecond, as we perform tasks or undergo different sleep stages. However, EEG is poor at attributing functions to specific brain regions. By far the most dominant imaging technology over the last two decades has been functional magnetic resonance imaging (fMRI), which can pinpoint neuronal activity changes to within a few millimetres and a few seconds. This is dramatically improving our understanding of the functional role of each brain region and how areas collaborate to support mental processes.
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Brain imaging allows us to study the shape, wiring and function of the human brain with great precision in a safe, non-invasive way.
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fMRI is starting to be used as a mind-reading device. So far, this is largely limited to estimating which of a small set of pictures, video snippets or words was just presented to an individual. But new methods are being developed that actually reconstruct perception by reading activity in the visual cortex and generating a fuzzy image from this. It is tantalizing to contemplate how far this form of technological telepathy will progress in the future.
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3-SECOND BIOGRAPHIES
HANS BERGER
1873–1941
Pioneer of EEG
PAUL LAUTERBUR
1929–2007
Pioneer of MRI
PETER MANSFIELD
1933–
Pioneer of MRI
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Daniel Bor
Other people can read your mind. Confirm your privacy settings by thinking only of primary colours and simple geometric shapes.
At whatever level you look, from the microscopic wires of a handful of neurons, up to the finger-thick fibres that connect major regions of cortex, the brain is essentially structured as a network. The entire map of all these networked wires is known as the connectome. Various ambitious, large-scale projects around the world are starting to piece together the human connectome from different angles. At the cellular level, much of this involves painstaking microscope work on tiny anatomical sections. Larger scale, though far cruder, methods include a form of MRI scanning technology called DTI (see here), which is designed to create an image of the brain’s major pathways non-invasively. One particular challenge in this global project is to knit together the various different techniques to create a coherent overall picture of the brain’s wiring. Although the activity of our many billions of neurons, along with our brain chemistry and genetics, are essential shapers of our mental world, many neuroscientists now think that this network structure is the most critical feature of all. The hope is that mapping the human connectome and exploring how it differs between people will reveal vital clues about our thoughts, the nature of psychiatric illnesses and, ultimately, who we are as mental beings.
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The human connectome is the entire map of all the 600 trillion wires in a human brain. We remain decades away from completing this project.
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Some believe that revealing the network structure of the human brain might yield fewer clues than promised, especially given that any connectome is continuously in flux as wires grow or die. One species in which the connectome has been largely complete for many years is that of the nematode worm, Caenorhabditis elegans. With a brain of just 302 neurons, it is one of the simplest animals, and yet many of its behavioural features remain a mystery.
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3-SECOND BIOGRAPHIES
DAVID VAN ESSEN
1945–
Leader of the Human Connectome Project and pioneer in neuroanatomy
CORNELIA BARGMANN
1961–
American neurobiologist known for her work on C. elegans
OLAF SPORNS
1963–
German scientist who coined the term ‘connectome’
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Daniel Bor
High-tech in the head. A two-dimensional rendition of a three-dimensional DTI image of some of the 600 trillion wires that power your brain.
In 1999 Francis Crick, the co-discoverer of DNA, mentioned some ‘farfetched’ ideas about genetically engineering neurons so that light alone could switch them on and off. He should have had more faith in his own field. Within five years, Karl Deisseroth and colleagues had used a virus to smuggle an algal light-sensitive gene into rat neurons. When exposed to a blue light, the neurons fired. Soon an ‘off’ as well as an ‘on’ switch was found. Another gene, this time from bacteria, could be added in a similar way, so neuronal firing could be suppressed whenever green light was shone on it. Now hundreds of labs around the world use similar techniques to probe the machinery of the brain with unprecedented control. Sometimes light can be shone from the surface, on the skull, but usually tiny emitters are implanted deep inside the brain. This technique can even be used to boost cognitive performance – Wim Vanduffel and colleagues recently modified a region of the frontal lobes in two monkeys to enable widespread light-induced activation. When a blue light turned this region on, the monkeys were faster at an object-tracking task. Therefore, as well as being one of the most innovative neuroscientific techniques of recent times, optogenetics holds great promise as a future clinical tool.
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Optogenetics involves genetically altering neurons, so that they can be precisely manipulated by using light to turn them on and off at will.
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What if you could immediately calm a raging storm of overactive epileptic neurons, just with a powerful lamp? Or take dormant movement-controlling cells that leave patients with Parkinson’s disease fighting just to make the simplest of movements and reinvigorate these neurons with an implanted micro-flashlight? Although significant safety concerns have to be met before human trials start, the potential applications for a wide range of psychiatric and neurological conditions are breathtaking.
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FRANCIS CRICK
1916–2004
First scientist to suggest optogenetics as a technique
KARL DEISSEROTH
1971–
Leading pioneer of the technique of optogenetics
ED BOYDEN
1979–
Collaborator with Deisseroth
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Daniel Bor
A pioneering brain surgeon and probably neuroscience’s greatest team player, Wilder Penfield was born in the USA and raised in Hudson, Wisconsin, but he claimed Canadian citizenship via his mother in 1934. He was a stalwart football star at Princeton (part of a career plan to gain a Rhodes Scholarship, which depended on a manly mixture of sporting and intellectual prowess) and spent a year after graduation as the team coach to help finance further study. Hard work and training paid off and in 1914 Penfield was awarded a Rhodes Scholarship to Merton College Oxford in England. He studied under neurophysiologist Charles Sherrington, who opened his mind to the uncluttered pastures of neuroscience, where there was much to be explored.
On his return to the USA, Penfield embarked on his career as a neurosurgeon, reasoning that he could better carry out research into the functions and secrets of the human brain if he had one under his scalpel. Penfield had a strong team ethic and philanthropic drive, apparently instilled by his mother. Instead of working alone, he envisaged an entire institute in which neuroscientists of all disciplines could work, research and learn together and share their findings for the betterment of humanity. The thinking at the time in New York did not suit this model, so he moved to the Medical Faculty of McGill University, from which base he lobbied energetically for funds, securing a grant from the Rockefeller Foundation. In 1934, he set up the Montreal Neurological Institute, which would become a powerhouse of neuroscientific research.
It was here that Penfield did the work on epileptic patients for which he is best remembered. He introduced the Montreal Method, in which he operated on patients to excise the parts of their brain from which epileptic seizures originated. He did this under local anaesthetic so that, invaluably, they could respond to his questions as he operated. His patients reported that when different parts of the brain were probed, they experienced different feelings and sensations. From the first-hand information gained, Penfield was able to make preliminary maps of the brain, establish the principle of brain lateralization and lay the foundations for future brain mapping. The stylized ‘homunculus’ that he produced with his colleague Herbert Jasper, in which the size of each body part reflects the number of nerves that serve it, is still in use today.
Born Spokane, Washington
1899
Moved with his family to Hudson, Wisconsin, his mother’s home
1913
Graduated from Princeton
1914–16
Rhodes Scholar at Merton College Oxford; studied neuropathology under Charles Sherrington
1918
MD from Johns Hopkins University; served apprenticeship under brain surgeon Harvey Cushing in Boston, Massachusetts
1919
Final year in Oxford as a Rhodes Scholar, followed by study in Europe
1921
Returned to USA to become Associate Surgeon at Columbia University
1928
Joined the Medical Faculty at McGill University
1934
Acquired funding for, founded and became director of the Montreal Neurological Institute (MNI), part of McGill University
1934
Became a Canadian citizen
1951
Wrote, with Herbert Jasper, Epilepsy and the Functional Anatomy of the Human Brain
1954
Retired from McGill Medical Faculty but continued as Director of the MNI
1960
Awarded the Lister Medal for contributions to surgical science
5 April 1976
Died in Montreal, Canada
In functional brain-imaging experiments, it is standard practice to give a volunteer a taxing task to perform while in the scanner and to associate the demands of the task with those parts of their brain that are observed to light up. But what happens in between those periods of effort? One might expect the brain’s activity to dramatically drop and some random firing pattern to ensue. The first clue that such assumptions are wrong came in the early 2000s from Marcus Raichle, who found that there is a consistent group of brain regions (known as the default mode network) whose activity is suppressed when we perform any focused task, but which springs back into action when we can mentally ‘twiddle our thumbs’. Around the same time, Michael Greicius uncovered the same set of regions when he took the bold step of deliberately scanning subjects when they were just resting. This striking clue about the brain’s activity is in a sense the ‘dark energy’ of neuroscience and researchers are still searching for an adequate account of it. One explanation is that it may be the neural signature of daydreams. Intriguingly, abnormalities in the default mode network are associated with a range of disorders, so perhaps this seemingly trivial pastime is far more important than we originally thought.
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Without a task to perform, the brain is almost as active as normal, but a ‘default’ set of regions lights up instead of task-related ones.
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The default mode network is delicately defined by the co-ordinated activity of a range of cortical areas, mainly located along the ‘cortical midline’ – where the hemispheres of the brain touch in the middle. A proper default mode takes years to emerge in infancy, and old age commonly disrupts it. Further evidence of the importance of the default mode network comes from its most promising putative role, that of daydreaming, which has been linked both to higher insight and creativity.
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3-SECOND BIOGRAPHIES
MARCUS RAICHLE
1937–
Discoverer of the default mode network
MICHAEL GREICIUS
1969–
Carried out pioneering studies of resting state
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Daniel Bor
Slackers rejoice! The brain is working almost as hard when you are staring into space as it does when you are looking busy.
Looking at a human brain, among the most obvious features is the fault line that runs along its centre from front to back, dividing the outer cortex into two distinct hemispheres. Although broadly anatomically symmetrical, the two halves don’t function in the same way. Nineteenth-century physicians, such as Paul Broca, realized this because patients with damage to the left side were far more likely to have language problems than those with damage to the right. Interest in the issue was re-ignited in the 1960s when Roger Sperry and others began investigating ‘split-brain’ patients, who’d had the thick bundle of nerves connecting their hemispheres cut to treat severe epilepsy. Testing these patients showed that the two hemispheres could operate independently and had different strengths and weaknesses. Today, it is popular to characterize the left hemisphere as cold and logical and the right as emotional and creative. This is an over-simplification. Split-brain patients aside, most people’s brain hemispheres work together. Instead of tasks being delegated to one side or the other, both hemispheres typically apply a different processing style to the same tasks. While the left hemisphere is dominant for language, the right has language functions of its own, including recognizing intonation.
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The two halves of the brain do work differently, but the notion of a creative right brain and logical left is an oversimplification.
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An industry of apps and self-help books has grown up around the idea of unlocking the right brain’s creative potential. There is evidence for right hemisphere creativity, but the left hemisphere is creative in its own way, too. Work with split-brain patients revealed the ‘interpreter phenomenon’ – the way the left hemisphere was very good at telling stories to explain what the left hand (controlled by the right hemisphere) was up to.
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ROGER SPERRY
1913–94
Won the Nobel Prize for his work with split-brain patients
MICHAEL GAZZANIGA
1939–
Trained with Sperry to pioneer split-brain experiments
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Christian Jarrett
Wilder Penfield, one of the most influential neurosurgeons of the 20th century (see here), would commonly operate on severely epileptic patients while they were conscious (operating on the brain itself causes no pain). In order to minimize the amount of brain tissue requiring excision, he pioneered the use of an electrical probe to stimulate neurons and determine more precisely if they were part of the main abnormality causing seizures. He soon discovered that this method was also useful for mapping the functions of different brain regions and reported, for instance, that stimulation of a single neuron in the temporal lobes would reactivate entire memories in the patient. Transcranial magnetic stimulation (TMS) is a popular modern successor to this technique. TMS is a non-invasive procedure that uses a brief magnetic pulse on the scalp to stimulate the underlying cortical region (roughly a square inch or so in size). Depending on the technique, this can raise, or more usually suppress, the region’s activity. If volunteers become better or worse at a particular task following TMS to a specific brain region, then this shows that the region is related to the corresponding process. In this way, TMS has become a useful additional tool to functionally map the brain.
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Neurons in specific locations can be electromagnetically stimulated, inducing changes in thought, perception or behaviour.
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Wilder Penfield also found that stimulating one neuron might make the patient think his right cheek had been touched; while stimulating another might make his left thumb twitch. By repeated stimulations, he discovered that the motor and sensory cortices form a very ordered map, for instance with tongue movements controlled on the lower outer cortical section. This arrangement, broadly the same for us all, is one of the most pronounced cortical examples of the localization of function.
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WILDER PENFIELD
1891–1976
Pioneered brain stimulation and discovered detailed neural sensory and motor maps
ANTHONY BARKER
1950–
First to use TMS in scientific research
JOHN ROTHWELL
1954–
Inventor of modern TMS technique to extend its effects by many minutes
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Daniel Bor
