Wednesday 29 April 2015

Peering directly into the human brain

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With the rise of non-invasive brain imaging such as functional magnetic resonance imaging (fMRI), researchers have been granted unprecedented access to the inner workings of the brain. It is now relatively straightforward to put your experimental subjects in an fMRI machine and measure activity 'blobs' in the brain. This approach has undoubtedly revolutionised cognitive neuroscience, and looms very large in people's idea of contemporary brain science. But fMRI has it's limitations. As every student in the business should know, fMRI has poor temporal resolution. fMRI is like a very long-exposure photograph: the activity snapshot actually reflects an average over many seconds. Yet the mind operates at the millisecond scale. This is obviously a problem. Neural dynamics are simply blurred with fMRI. However, probably more important is the theoretical limit.

Wiki in ECoG
Electricity is the language of the brain, but fMRI only measures changes in blood flow that are coupled to these electrical signals. This coupling is complex, therefore fMRI can only provide a relatively indirect measure of neural activity. Electroencephalography (EEG) is a classic method for measuring actual electrical activity. It has been around for more than 100 years, but again, as every student should know: EEG has poor spatial resolution. It is difficult to know exactly where the activity is coming from. Magnetoencephalography (MEG) is a close cousin of EEG. Developed more recently, MEG is better at localising the source of brain activity. But the fundamental laws of physics mean that any measure of electromagnetic activity from outside the head will always be spatially ambiguous (the inverse problem). The best solution is to record directly from the surface of the brain. Here we discuss the unique opportunities in that arise in the clinic to measure electrical activity directly from the human brain using electrocorticography (ECoG).

Epilepsy can be a seriously debilitating neurological condition. Although the symptoms can often be managed with medication, some patients continue to have major seizures despite a cocktail of anti-epileptic drugs. So-called intractable epilepsy affects every aspect of life, and can even be life-threatening. Sometimes the only option is neurosurgery: careful removal of the specific brain area responsible for seizures can dramatically improve quality of life.

Neurosurgery
Psychology students should be familiar with the case of Henry Molaison (aka HM). Probably the most famous neuropsychology patient in history, HM suffered intractable epilepsy until the neurosurgeon William Scoville removed two large areas of tissue in the medial temporal lobe, including left and right hippocampus. This pioneering surgery successfully treated his epilepsy, but this is not why the case became so famous in neuropsychology. Unfortunately, the treatment also left HM profoundly amnesic. It turns out that removing both sides of the medial temporal lobe effectively removes the brain circuitry for forming new memories. This lesson in functional neuroanatomy is what made the case of HM so important, but there was also a important lesson for neurosurgery – be careful which parts of the brain you remove!

The best way to plan a neurosurgical resection of epileptic tissue is to identify exactly where the seizure is comping from. The best way to map out the affected region is to record activity directly from the surface of the brain. This typically involves neurosurgical implantation of recording electrodes directly in the brain to be absolutely sure of the exact location of the seizure focus. Activity can then be monitored over a number of days, or even weeks, for seizure related abnormalities. This invasive procedure allows neurosurgeons to monitor activity in specific areas that could be the source of epileptic seizures, but also provides a unique opportunity for neuroscientific research.

From Pasley et al., 2012 PLoS Biol. Listen to audio here
During the clinical observation period, patients are typically stuck on the hospital ward with electrodes implanted in their brain literally waiting for a seizure to happen so that the epileptic brain activity can be ‘caught on camera’. This observation period provides a unique opportunity to also explore healthy brain function. If patients are interested, they can perform some simple experiments using computer based tasks to determine how different parts of the brain perform different functions. Previous studies from some of the great pioneers in neuroscience mapped out the motor cortex by stimulating different brain areas during neurosurgery. Current experiments are continuing in this tradition to explore less well charted brain areas involved in high-level thought. For example, in a recent study from Berkeley, researchers used novel brain decoding algorithms to convert brain activity associated with internal speech into actual words. This research helps us understand the fundamental neural code for the internal dialogue that underlies much of conscious thought, but could also help develop novel tools for providing communication to those otherwise unable to general natural speech.


From Dastjerdi et al 2013 Nature Communications (watch video below)

In Stanford, researchers were recently able to identify a brain area that codes for numbers and quantity estimation (read study here). Critically, they were even able to show that this area is involved in everyday use for numerical cognition, rather than just under their specific experimental conditions. See video below.
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The great generosity of these patients vitally contributes to the broader understanding of brain function. They have dedicated their valuable time in otherwise adverse circumstances to help neuroscientists explore the very frontiers of the brain. These patients are true pioneers.





Key References

Dastjerdi, M., Ozker, M., Foster, B. L., Rangarajan, V., & Parvizi, J. (2013). Numerical processing in the human parietal cortex during experimental and natural conditions. Nat Commun, 4, 2528.


Pasley, B. N., David, S. V., Mesgarani, N., Flinker, A., Shamma, S. A., Crone, N. E., Knight, R. T., & Chang, E. F. (2012). Reconstructing speech from human auditory cortex. PLoS Biol, 10, e1001251.


Video showing the use of a number processing brain area in everyday use:



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