Download The mind and brain are an inseparable unit.

WEEK ONE: HOW DOES THE BRAIN WORK? | ESSAY THREE
Mind in the Brain
By Dr. Joy Hirsch
The mind and brain are an inseparable unit.
This amazing idea is the foundational principle of current neuroscience.
In The Astonishing Hypothesis, Francis Crick eloquently illuminates this
fundamental principle: "You, your joys and your sorrows, your memories and
your ambitions, your sense of personal identity and free will, are, in fact, no
more than the behavior of a vast assembly of nerve cells and their
associated molecules." As Lewis Carroll’s Alice might have phrased it:
"You’re nothing but a pack of neurons."
This notion is potentially as powerful as Crick’s earlier discovery of the
molecular structure of DNA and the genetic code that builds each of us.
However the basic mechanisms that couple biology and behavior remain a
relative frontier in science. That intimate coupling between molecules, cells,
circuits and behavior is evident, for example, in the notable discoveries of
the molecular basis of memory and smell by Eric Kandel and Richard Axel
who each received recent Nobel prizes for these advances. Widespread and
growing acceptance of this notion is also evident in the “neurocentric”
vocabulary that enriches our everyday language with words like
neuromarketing, neuroeconomics, neuropolitics, neurophilosophy,
neuroethics, and neurolaw. As suggested by these hybrid words, the
behavior of neurons is incorporated into mainstream conversation and
thought, and traditional academic disciplines can now be considered “life
sciences.” This includes disciplines such as economics, law, business,
finance, marketing, and psychology, in addition to the traditional medical
disciplines of neurology, psychiatry, surgery, medicine and radiology. New
sciences have also emerged. The decision sciences, for example, have the
potential to enhance our understanding of topics such as “personal identity
and free will” in terms of executive control, and biases in situations of
uncertainty and risk based on the behavior of neural systems.
On the “home front,” this new neurocentric view has many advantages. We
now have new cognitive tools to cope with everyday anxieties such as taking
a plane or getting stuck in an elevator. These tools can be used to say
“amygdala be still” when anxiety strikes. Motivation to resist a chocolate
chip cookie can be conceptualized by recalling a neural model of cognitive
control that translates this temptation into a “tug-of-war” between reward
and executive control systems. From this point of view, a “tug” from the
executive control branch of neural systems increases resistance to the
tempting power of chocolate chip cookie. Answering a phone, reading email, and navigating life’s treacherous political landscapes become the
putative handiwork of “a vast assembly of neurons” purposed for executive
functions.
Along the same lines, this astonishing hypothesis provides a context for
important personal decision-making, such as choosing a life partner. For
example, the “vast assembly of nerve cells and their assorted molecules”
sprinkled with various neurochemical cocktails in my basal ganglia are
presumably the basis for my love and attachment to my husband. Earlier in
my academic journey I would have resisted this biological perspective on the
grounds that a physical basis for such a complex life choice would diminish
its grandeur and centrality. This dismissive view of the role of neurons
relating to the quality of human experience is common in our culture.
Crick’s rephrasing of Lewis Carroll’s famous quote--“You’re nothing but a
pack of neurons” -- implies that a biological basis somehow diminished the
value and meaning of our emotions and feelings. Emerging advances in
neuroscience have not erased this notion, but have embraced the challenge
of integrating neural machinery as an underpinning for behavior and
emotion. However, we are now challenged to understand how the workings
of a brain actually create “joys and sorrows and memories and ambitions,
personal identity and free will” as well as shared love between life partners.
This is the goal of the new “science of mind.”
Science of mind starts with wonder: how can a “pack of neurons” achieve the
biological perfection that yields the essence of our humanity, attachments,
and inner lives? We have long been aware that feelings begin as signals from
the outside world that bombard sensory systems with packets of energy. For
example, sound pressure energy on the eardrums is transduced by delicate
membranes in our inner ear and then communicated to neurons in Heschl's
gyrus to create the foundation for the experience of sound. Further
processing of those neural signals leads to language, music, meaningful
information, and even emotions. Specialized neurons in the back of the eye
convert energy from photons within a specific range of radio frequencies
into the perception of light, and then to color, shape, objects in scenes, and
visual contexts that meaningfully connect us to the visible world. Similarly,
the smell of coffee starts as an airborne molecule that is captured by
dedicated neurons in the epithelial layer of nasal passages and converted to
a delightful aroma. The unrestrained joy conveyed by wet and cold kisses
from a dog who has been waiting all day for you to return starts with
mechanical receptors in the face and hands. Those receptors signal sensory
motor neurons to start an orchestra of neural signals to generate visual,
auditory, and emotional components that integrate to convey a moment of
unconditional love.
Yes, at the root of who we are and how we experience the universe, neurons
rule. But how do they do it? Historically, quantum leaps in science have been
made in conjunction with advances in imaging technology. The microscope
enabled views of infinitely small subunits of life forms, and the telescope
enabled views of infinitely large solar systems. Each extended the
boundaries of the human eye and mind, and our scientific understanding of
the principles that govern life and the universe.
Current brain imaging technology is equally revolutionary. Functional MRI
(fMRI) provides views of the brain while dynamically engaged, enabling
neuroscientists to discover the relationships between specific mental
operations and the associated working parts of the brain.
Although a relatively new discipline, functional neural imaging has taken us
far into the unknown territory of the biology that underlies who we are,
altering how we think about ourselves and each other. I think of this
technology as a “mindoscope”, a “scope” to reveal the mind in the landscape
of the brain. It marries two disciplines: imaging sciences and behavioral
sciences. A conventional MRI uses a magnetic resonance signal to reveal the
structure of a living human brain. Functional MRI uses the same signal to
track oxygen levels in the blood, and, because active neural tissue consumes
more metabolites than resting neural tissue and uses more oxygen,
increases in the flow of oxygenated blood indicate neural activity. This
occurs when the brain is engaged during a specific task. Figure 1 shows a
research volunteer preparing for a functional imaging study of the languagesensitive regions of the brain.
Figure 1. Functional MRI study
A research subject is shown preparing to go into the Hirsch Laboratory fMRI
scanner at Columbia University School of Medicine. The task that he will
perform while in the scanner is to silently name the pictures (illustrated on
the side panels) as they are presented to him via a back projection screen.
The object naming task employs “internal or silent speech” to avoid the head
movements associated with spoken speech. The pictures are presented in 15
second blocks that alternate with 15 second rest epochs. ©AMNH
Enlarge image »
Findings from functional imaging studies are commonly represented as
yellow and orange points and clusters of points on magnetic images of the
brain. These colors identify active regions and become the data for neural
imaging studies. Figure 2 illustrates this process. Functional magnetic
resonance imaging, fMRI, exploits the most fundamental principle of brain
organization, the “real estate” principle: specific clusters of neurons perform
specific types of functions. The biology that underlies the roots of conscious
experience including perception, thought, and actions, is isolated by
experiments that selectively engage specific neural tissue called to action
during specific functional tasks. Carefully designed experiments enable
scientists to test hypotheses about the mechanisms of signaling between
coordinated brain areas. Figure 3 illustrates a few of the well-known
functional specificities of brain regions, and much current research is now
focused on how these areas communicate to share information.
Figure 2. Active areas of the brain
The left panel shows an image representing a horizontal slice (axial section)
of the subject’s brain. The top of the image is the front of the brain and the
right of the image in the left hemisphere. The grid represents the resolution
of the image where the voxel (volume element) is 1.5 x 1.5 mm. Each grid
box in the figure represents a 5 x 5 array of voxels. The yellow and red
regions represent voxels with MR signals that statistically exceed baseline
(rest) levels during the object naming task relative to the signal during rest.
The panel on the right illustrates such a signal from a single voxel located at
(x = 90, y = 35) which is located in the inferior frontal gyrus, left
hemisphere, an area known as Broca’s Area as indicated by the label. Broca’s
Area is known as a region associated with speech production and language
comprehension. ©Joy Hirsch
Enlarge image »
Figure 3. Brain regions with well-known functions
A general illustration of the important principle of functional specialization
where specific areas of the brain are specialized for specific functions. This
illustration shows the left hemisphere and includes the area specialized for
speech production (as illustrated in a real image in Figure 2). In truth the
regional specializations are observed on a much finer grain than suggested
by this graphic. ©AMNH/Richard Tibbits
Enlarge image »
Does this explain, “how they do it?” Every neuroimaging tool—including
functional magnetic resonance imaging (fMRI), positron emission
tomography (PET), electroencephalography (EEG), magnetoencepheography
(MEG), and optical imaging—is limited. Many of the hardest questions, like
how neurons turn energy packets captured from the environment and
absorbed by neural transducers into conscious experience remain beyond
our reach at the present time. Nonetheless, current “mindoscopes” segment
the healthy brain according to task-related systems. When coupled with
rigorously designed experiments, these systems reveal dynamical
mechanisms of top-down and bottom-up pathways that influence one
another to execute tasks and modulate performance. For example, scientists
have recently applied fMRI to discover within-brain processes that modulate
behavior, revealing mechanisms that suppress emotional responses, boost
detection processes, improve focus on cognitive tasks, and resolve conflict.
Several examples of these findings are included in the bibliography at the
end.
A floodgate of new opportunities to advance how we think about ourselves
and our behavior has opened as a result of functional brain imaging studies,
and ultimately will translate into advances in patient care and quality of life.
A few examples follow. Eating disorders, obesity, and addictions can be
studied in terms of the neural circuitry sensitive to reward and executive
control. Anxiety disorders and post-traumatic stress may be diagnosed,
prevented, and treated by image-guided approaches that reveal the circuitry
related to fear. Functional image guided methods may lead to better
diagnosis and treatment of developmental disorders such as autism. Figure
4 illustrates ways in which the language system in autistic brains differs
from that of typical brains. Note the reduction of brain activity in the frontal
areas of autistic subjects. Psychiatric disorders, including dementia,
schizophrenia, depression, obsessive-compulsive, and panic disorders may
also be diagnosed by characteristic patterns of the neural circuitry, which
will inform personalized treatment strategies. Patients whose traumatic
brain injury has caused disorders of consciousness can be “given a voice” by
reading brain responses to specific passive stimulations or task-related
requests.
Figure 4. Horizontal (axial) and side (sagittal) views of group images
for typical (control) and autistic children
Of note is the neural activity within the circled regions that highlight Broca’s
Area in left Inferior Frontal Gyrus, LIFG of both sets of images. The children
were all age-matched and hearing normal and all participated in an fMRI
experiment where they passively listened to a recording of a parent talking
to them. Control subjects demonstrate robust activity in LIFG in response to
listening to the speech whereas the homologous regions in the autistic
children did not respond. These data are consistent with an emerging
consensus that neural information processing in autism involves reduced
representation in frontal lobe structures for spoken language. ©Joy Hirsch
Enlarge image »
The applications extend beyond frontiers in medicine. Neural systems
engaged when healthy individuals make economic decisions respond with
biases related to fear, emotional arousal, and losses and gains. This could
alert financial managers to risky or problematic financial decisions. Value
and preference may have neural underpinnings, as well as political attitudes,
prejudices, and moral judgments. Learning may be guided by neural
tendencies, and compensatory mechanisms for memory loss may be neurally
guided and strategically enhanced. Even political policy may be thought of in
terms of neural responses to variables such as altruism, personal comfort,
and perceived safety. The transformative effects of art, poetry and music
may also be credited in part to contributions from gifted neurons endowed
with complex abilities to connect highly valued stimuli to neural emotiongenerators in the brain. The bibliography also includes a few examples of
these findings.
As these examples suggest, we can expect a vast array of questions,
insights, and medical advances to emerge from the teams of scientists,
physicians, and students joined together in the discovery of brain processes
that define our humanity. In the context of this new scientific framework and
based on the astonishing unity of brain and behavior, we all become
students and together travel the “neurojourney” along the road to the mind.
This journey leads us to unprecedented opportunities to understand
ourselves as wondrous works of nature in which fertile packs of neurons are
responsible for a human spirit bursting with creativity, love, beauty, joys,
and sorrows. Moment by moment thoughts, sensations, and actions emerge
as if they were a bouquet of flowers from the garden of brain.
An earlier version was published by the author in Portraits of Mind (edited
by Carl Schoonover and published by Abrams, Chapter 7, 200-227, 2010) as
a chapter titled “From Brain Structure to Brain Function.”
Joy Hirsch, Ph.D. is Professor of Psychiatry and Neurobiology at Yale
University School of Medicine
REFERENCE BIBLIOGRAPHY
Recommended as supplemental reading:
Lai, G., Pantazatos, S.P., Schneider, H., Hirsch, J., Neural systems for speech
and song in autism, Brain, 2012 Mar, 135(Pt 3):961-75.
Summerfield, C., Egner, T., Greene, M., Korchlin, E., Mangels, J., Hirsch, J.,
Predictive Codes for Forthcoming Perception in the Frontal Cortex, Science
(111, v.314, no.5803, 1311-1314), 2006.
Egner, T., Hirsch, J., Cognitive control mechanisms resolve conflict through
cortical amplification of Task-Relevant information, Nature Neuroscience, 8
(12), 1784-1790, 2005
Hirsch, J., Ruge, M.I., Kim, K.H.S., Correa, D.D., Victor, J.D., Relkin, N.R.,
Labar, D.R., Krol, G., Bilsky, M.H., Souweidane, M.M., DeAngelis, L.M., Gutin,
P.H. An Integrated fMRI Procedure for Preoperative Mapping of Cortical Areas
Associated with Tactile, Motor, Language, and Visual Functions.
Neurosurgery, 2000, 47(3), 711-722.
Kim, K.H.S., Relkin, N.R., Lee, K.M., Hirsch, J. Distinct cortical areas
associated with native and second languages. Nature, 1997, 388, 171-174.
Recommended for special interests related to the subjects discussed in
the text:
Karten A, Pantazatos S, Khalil D, Zhang X, Hirsch J. Brain Connectivity.
Dynamic Coupling between the Lateral Occipital Cortex, Default Mode and
Frontoparietal Networks During Bistable Perception. Brain Connectivity,
2013. doi:10.1089/brain.2012.0119.
Pannese, A., Hirsch, J., Unconscious neural specificity for “self” and the
brainstem, Journal of Consciousness Studies, 2013. Journal of
Consciousness Studies, Volume 20, Numbers 1-2, 2013, pp. 169-179(11)
Zhang, X., Hirsch, J., The temporal derivative of expected utility: a neural
mechanism for dynamic decision-making, NeuroImage, 2013 Jan 15, 65:22330.
Pantazatos, S.P., Talati, A., Pavlidis, P., Hirsch, J. Cortical functional
connectivity decodes subconscious, task-irrelevant threat-related emotion
processing, Neuroimage, 2012 Mar 28, 61(4):1355-1363.
Lai, G., Schneider, H., Schwarzenberger, J., Hirsch, J. Speech stimulation
during functional MR imaging as a potential indicator of autism. Radiology,
260(2):521-530, 2011 August.
Rodriguez-Moreno, D., Hirsch, J., Giacino, J., Schiff, N., Kalmar, K. A network
approach to assessing cognition in disorders of consciousness. Neurology,
75(21):1871-1878, 2010. PMID: 20980667.
Rodriguez-Moreno, D., Hirsch, J. The Dynamics of deductive reasoning: an
fMRI investigation, Neuropsychologia, 47: 949-961, 2009. PMID: 18835284.
Rosenbaum, M., Sy, M., Pavlovich, K., Leibel, R., Hirsch, J. Leptin reverses
weight loss– induced changes in regional neural activity responses to visual
food stimuli, Journal of Clinical Investigation, 118(7): 2583-2591, 2008.
PMID: 18568078. PMCID: PMC2430499.
Kelly, C., Grinband, J., Hirsch, J. Repeated exposure to media violence is
associated with diminished response in an inhibitory frontolimbic network,
PloSONE, 2(12): e1268. Doi:10.1371/journal.pone.0001268, 5 December
2007.
Wang, Y., Lin, L., Kuhl, P., Hirsch, J., “Mathematical and linguistic processing
in native and second languages,” Brain Imaging and Behavior, 2007; 1: 6882.
Kross, E., Egner, T., Ochsner, K., Downey, G., Hirsch, J., Neural dynamics of
rejection sensitivity, Journal of Cognitive Neuroscience, 2007; 19(6): 945956.
Etkin, A., Egner, T., Peraza, D.M., Kandel, E.R., Hirsch, J., Resolving
emotional conflict: a model for amygdalar modulation by the rostral anterior
cingulate cortex, Neuron, 51, 871-882, 2006.
Grinband, J., Hirsch, J., Ferrera, V.P., A neural representation of
categorization uncertainty in the human brain, Neuron, 2006, 49: 757-763.
Schiff, N.D., Rodriguez-Moreno. D., Kamal, A., Kim, K.H.S., Giacino, J.T.,
Plum, F., Hirsch, J. fMRI Reveals Large Scale Network Activation in Minimally
Conscious Patients, Neurology, 2005, Vol 64, 514-523.
Nuñez, J.M., Casey, B. J., Egner, T., Hare, T., Hirsch, J., Intentional False
Responding Shares Neural Substrates With Response Conflict and Cognitive
Control, NeuroImage, 2005, Vol 25, 267-277.
Etkin, A., Klemenhagen, K., Dudman, J., Rogan, M., Hen, R., Kandel, E.,
Hirsch, J. Individual Differences in Trait Anxiety Predict the Response of the
Basolateral Amygdala to Unconsciously Processed Threat, Neuron, 2004, Vol
44, 1043-1055.
Lai, G., Pantazatos, S.P., Schneider, H., Hirsch, J., Neural systems for speech
and song in autism, Brain, 2012 Mar, 135(Pt 3):961-75.