Hebrew University: Brain’s Mysteries Involving Alzheimer’s And ‘Brain Maps’ Resolved

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“By combining direct clinical involvement and cutting-edge computational methods, we are able to reframe neuropsychiatry and to develop effective patient-tailored clinical tools."

The human brain

Hebrew University researchers have used a mathematical algorithm and smartphone applications to unravel a longstanding mystery relating to a basic property of the brain and better understand Alzheimer’s disease.

Neuroscientist Dr. Shahar Arzy, director of the computational neuropsychiatry lab and colleagues from the Edmond and Lily Safra Center for Brain Sciences have just published their findings in Proceedings of the National Academy of Sciences (PNAS).

It has long been known that the brain uses topographic organization, meaning that parts of the brain make “spatial computation” or “brain maps,” as well as similar types situated close to each other.

But in the case of brain disease, these topographies may undergo reorganization. The researchers now show that it is the continuity of these brain maps that is disturbed.

Moreover, this continuity can be quantified, allowing them to be used as a biomarker for detecting neuropsychiatric disease.

Using functional MRI (fMRI), they studied two types of unique patient populations: patients with injury to one side of the spinal cord, which enabled comparison of disturbed and non-disturbed body sides, and patients undergoing surgical repair.

“Behavioral and functional neuroimaging examination of this system may therefore enable early detection of Alzheimer’s disease far before clinical signs are evident, which is crucial for presentation of preventive treatment,” said Arzy. The researchers have already tested their hypothesis in patients and designed an Android-based app for the developed test.

“This approach made it possible to directly compare human patients with respect to their own self or before and after surgical intervention. Instead of inducing lesions in animals, the team could repair the human patients and check them before and after. Importantly, unlike animals, patients could report their subjective experience, which is crucial for understanding high cognitive functions and neuropsychiatry.”

The researchers developed an algorithm that quantifies continuity of the patients’ brain maps. Their results showed that in each patient, pathological processing was reflected by a discontinuity of topographic maps rather than signal reduction.

“These findings suggest that continuity is a primary principle in brain computation, but in pathological states. The brain may give up on this principle to retrieve as much information as possible,” said Arzy. “Moreover, this may serve as a biomarker for neurological pathologies that we are now investigating.”

The researchers are now fine-tuning their findings in neurosurgical patients to enable a better patient-tailored diagnosis and follow- up. They are also extending their findings to other kinds of brain processing such as vision, hearing, number processing and memory.

Earlier this year, the HU team published research in PNAS that earned them “best scientific paper award” from the Israeli Neurological Association for 2015. In it, they solved another mystery – the brain function that relates the behaving self to the environment, what they call “mental-orientation.”

Through high-resolution fMRI scanning, the team showed that mental orientation in space, time and person produces a sequential and partially overlapping posterior-anterior pattern of activity in the brain.

Based on these findings, the researchers showed that mental orientation is managed by a specific brain system with a highly ordered internal organization. The researchers hypothesized that it is this mental-orientation system that is disturbed in Alzheimer’s disease.

The lab, located in both the HU-Hadassah Medical School and the Hadassah University Medical Center’s neurology department, combines clinical practice and research in neurology, psychiatry, computer science, physics and psychology. It also applies state-of-the-art computational methods on rare clinical data, allowing researchers to perform sophisticated analyses and modeling and improve scientific understanding of the human self in health and in disease.

“Our main interests involve epilepsy, neurodegenerative diseases, conversive and dissociative disorders, amnesias, disorientation states and different cognitive disturbances and misperceptions,” said Arzy. “By combining direct clinical involvement and cutting-edge computational methods, we are able to re-frame neuropsychiatry and at the same time to develop effective patient-tailored clinical tools, which fits the new digital era of computational revolution and precision medicine.”

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