Substantia. An International Journal of the History of Chemistry 1(1): 25-36, 2017

Firenze University Press 
www.fupress.com/substantia

DOI: 10.13128/Substantia-11

Citation: C.L. Khetrapal, K.V. Ram-
anathan (2017) Title. Substantia 1(1): 
25-36. doi: 10.13128/Substantia-11

Copyright: © 2017 C.L. Khetrapal, 
K.V. Ramanathan.This is an open 
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evant data are within the paper and its 
Supporting Information files.

Competing Interests: The authors 
declare no competing interests.

Feature Article

Developments of NMR - From Molecules to 
Human Behaviour and Beyond

C.L. Khetrapal1* and K.V. Ramanathan2

1Centre for Biomedical Research, Sanjay Gandhi Post Graduate Institute of Medical Sci-
ences Campus, Raebareli Road, Lucknow 226 014, India 
2NMR Research Centre, Indian Institute of Science, Bangalore 560012, India
Corresponding author. E-mail: clkhetrapal@hotmail.com

 
Abstract. NMR has made rapid progress in the last more than seven decades 
after its discovery. This article reviews the development of this field over the 
years with emphasis on some of the recent developments with interesting con-
sequences for the study of mental health and human behaviour. 

Keywords. NMR, MRI, fMRI, Molecular structure, Brain imaging

INTRODUCTION

Nuclear Magnetic Resonance (NMR) is perhaps the only field which has 
produced seven Nobel Laureates till date in all the disciplines of science in 
which the prize is given, in a short span of about seventy years from the 
discovery of the phenomenon. Over this period, it has thus established itself 
as a full-fledged interdisciplinary science rather than being just an analyti-
cal technique. Its utility has been fully exploited by physicists, chemists, 
biologists, clinicians, agriculturists, industrialists, computer scientists, psy-
chologists and social scientists. The developments of the field up to 1996 
are described in the eight-volume Encyclopaedia of NMR1 published in the 
year 1996 to commemorate 50 years of the discovery of the phenomenon. 
The growth of the field has been so voluminous that a supplementary 9th 
volume of the encyclopaedia had to be published within 5 years of the ini-
tial publication.2 This presentation gives a brief description of the field over 
these years from the perspective of the authors. The articles published by 
the authors earlier have been liberally used. Developments of the field ‘at a 
glance’ are presented in Fig.1.

NMR IN BULK MATERIAL

Purcell in MIT/Harvard and Bloch in Stanford became interested in 
experiments leading to accurate measurements of magnetic fields/magnetic 



26 C.L. Khetrapal and K.V. Ramanathan

moments. Both the groups succeeded and NMR in Bulk 
materials was born in 1945 and the results published in 
the same issue of the Physical Review.3,4 Both the sci-
entists got the Nobel Prize in Physics in 1952. NMR in 
India started in 1951 with the first report of NMR experi-
ments carried out in flowing liquids by Suryan5 who 
demonstrated that the arrival of fresh polarized sample 
at the RF coil decreases saturation and results in a more 
intense NMR signal. He was able to estimate Spin – lat-
tice relaxation time (T1) from the flow rate and the geo-
metrical parameters of the system.

NMR IN CHEMISTRY

Proton Chemical Shifts: Dramatic observation6 of 
separate lines for non-equivalent protons in the same 
molecule, by Arnold, Dharmatti and Packard in 1951 set 
the stage for most of the applications of NMR in various 
branches of sciences dealing with structural studies. The 
first molecule to be studied was acetic acid and then ethyl 

alcohol (Fig. 2). This led to the discovery of ‘Chemical 
Shifts’ in protons and it formed the basis of most of the 
applications of NMR.

Indirect Spin-Spin Couplings: This is another param-
eter which is of great significance in structural studies. 

Figure 1. Developments of NMR at a glance.

DEVELOPMENTS	OF	NMR	–	AT	A	GLANCE	

DISCOVERY	IN	BUL	MATERIAL	
1945-1946	

CHEMICAL	SHIFT	1950	
COUPLING	CONSTANT	1951	

RELAXATION	PROCESSES	1946	SOLIDS	STRUCTURE	AND	
MOTION	1948	

CHEMICAL	APPLICATIONS	1951	
EXCHANGE	PROCESSES	1953	

PULSE	EXPERIMENTS:	
SPIN	ECHOES	1950	

QUADRUPOLE	SPLITTINGS	1950	

INTERPRETATION	OF	COMPLEX	
SPECTRA	1953	

NUCLEAR	OVERHAUSER	EFFECT	
1953	

MAGIC	ANGLE	SPINNING	
1958-1959	

NEW	ERA	

NEMATIC	LIQUID	CRYSTALS	
IN	NMR	1963	

MULTIPULSES	1968	IMAGING	1973	FT-NMR	1966	

NEW	DIMENSIONS	TO	
MOLECULAR	STRUCTURES	

1964	

STRUCTURE	IN	THE	SOLID	
STATE:	MATERIAL	SCIENCE	

CLINICAL	APPLICATIONS	MULTIDIMENSIONAL	NMR	
1971	

MEMBRANE	STUDIES	1971	 POLYMERS	FUNCTIONAL	IMAGING		BIOMOLECULAR	STRUCTURE	
METABOLIC	STUDIES	

DIRECT	RELEVANCE	TO	
SOCIETY		

3-DIMENSIONAL	STRUCTURE	
OF	BIOMOLECULES	

FUTURE	HORIZONS:	
(1)  CLINICAL	APPLICATIONS	
(2)  MIND	READING	
(3)  ULTRA	LOW	FIELD	NMR	

Figure 2. First reported proton NMR spectrum 1 spectrum of ethyl 
alcohol. Reprinted from Ref. 6, with the permission of AIP Publishing.



27Developments of NMR - From Molecules to Human Behaviour and Beyond

Unlike Chemical Shifts, it is field-independent. It is diffi-
cult to establish unequivocally the real discoverer of Spin-
spin Couplings; at least the following three groups can be 
considered independently responsible for its observation. 
1. Arnold, Dharmatti and Packard did get the indica-

tion of some fine structure as line-distortion particu-
larly in the methyl peak in their original spectrum of 
ethyl alcohol (Fig. 2) but this distortion went unno-
ticed.

2. Gutowsky and Hoffman observed 2 lines of compara-
ble intensity in the 19F spectrum of PF3.7

3. Hahn and Maxwell observed the same effect in 
entirely different manner – as ‘slow-beats’ in the 
spin-echo envelope for non-equivalent protons8.
In structural studies, the spin-spin couplings have 

been extensively employed to estimate the dihedral angles 
using Karplus equations.9 The couplings for protons on 
adjacent saturated carbons (JVicinal) can be employed to 
estimate the dihedral angles within a precision of a few 
degrees using the following empirical equations: 

(JVicinal) = 8.5 cos2 j-0.28 Hz (for 0°<j<90°)
(JVicinal) = 9.5 cos2 j-0.28 Hz (for 90°<j<180°)

NEW ERA IN NMR

The following discoveries changed the destiny of 
NMR and the field entered a new era.
1. Fourier Transform NMR (1965-66)
2. Two-dimensional NMR (1971-72)
3. Magnetic Resonance Imaging (1973-74)

Fourier Transform NMR: The development of Fou-
rier transform methods10 represents a turning point in 
the history of NMR. In an NMR experiment at a particu-
lar magnetic field strength (Bo), the angular frequency 
of precession (ωo) of the nuclei is given by the Larmor 
equation ωo = γBo where the proportionality constant γ 
is the magnetogyric ratio ( ratio of the magnetic moment 
to the angular momentum). In a conventional continu-
ous wave NMR experiment, the resonance condition is 
arrived at either by keeping the frequency of irradiation 
fixed while varying the magnetic field fixed or vice versa. 
Such slow scan experiments were of limited utility espe-
cially for studies of solutions with low concentrations of 
the nuclei of interest, nuclei with low natural abundance, 
larger molecules, fast dynamic processes and so on. Even 
as efforts to improve the sensitivity of the NMR experi-
ment were in progress, to speed up the experiment Ernst 
and Anderson10 suggested the use of the Fourier trans-
form method. Herein, a short burst of radiofrequency 

(r.f.) excitation, called a pulse of r.f., excites nuclear spin 
resonances over a broad band of frequencies. The preces-
sion of nuclear spins having resonance frequencies falling 
in this band-width generates the NMR signal in the time 
domain. Subsequent Fourier transform of the signal pro-
vides the frequency domain NMR spectrum. This inno-
vation changed NMR signal acquisition from frequency-
domain to time-domain and thus on the one-hand made 
the NMR experiment faster by several-folds. On the 
other-hand, it opened up the flood-gates for innovation 
in NMR and the possibility of carrying out a whole lot of 
new experiments. Thus a new era of research and applica-
tions of NMR was born. Though difficult to publish the 
results at the time, the experiment formed the basis of 
the 1991 Nobel Prize in Chemistry to Richard Ernst.

Two –dimensional NMR: The concept of two-
dimensional (2D) Fourier transform NMR was given by 
the Belgian Physicist J. Jeener who presented his results 
at Ampere International Summer School, in 1971.11 He 
proposed a simple sequence of two 90° pulses separated 
by a time period t1which is incremented between the 
experiments. This is followed by double Fourier trans-
formation of the signal acquired after the second pulse. 
A spectrum is thus obtained which has spread in two 
frequency dimensions and for homonuclear experi-
ments has diagonal as well as cross peaks. The cross 
peaks carry important information as they result due 
to magnetization transferred from one nuclear spin 
species to another that has an indirect spin-spin cou-
pling to it. The results were never published formally. 
The school was attended by Thomas Bauman of Rich-
ard Ernst’s group. When briefed by Baumann, Ernst 
was very excited but still did not pursue the idea for 
quite some time since firstly he considered it as “Jeen-
er’s Property” and secondly he did not have a computer 
adequate to handle the two-dimensional data storage 
and processing. Eventually, he applied the concept to 
a different area namely magnetic resonance imaging 
(vide below) initially and later on published a series of 
papers that formed the foundation of two-dimensional 
NMR as a methodology.12

Magnetic Resonance Imaging (MRI): Paul Lauterbur 
conceived the idea of using magnetic field gradients to 
obtain 2 and 3 dimensional spatial information about the 
distribution of magnetic nuclei in a sample placed inside 
NMR coil. He thus created the picture of the object by 
NMR and called the technique as Zeugmatography. He 
published the work in Nature13 in 1973 and also submit-
ted it as a poster presentation at the triennial conference 
of the International Society of Magnetic Resonance held 
in Bombay in 1974. The presentation was however, con-
verted into an invited plenary talk by the organizers.



28 C.L. Khetrapal and K.V. Ramanathan

MRI is based on the principles of NMR but instead 
of revealing structures of molecules, MRI reveals the 
structure of an object, by mapping the distribution of a 
molecule (usually water) in the object. MRI’s most suc-
cessful and well known application is in the field of medi-
cine where it is used to image organs of a human body in 
microscopic details. In human MRI, a person lies inside 
a large hollow magnet. With a combination of magnetic 
field gradients and radio waves, signals are produced. 
A computer converts these signals into a series of 2-D 
images. The images can then be combined to create high-
resolution 3-D pictures of the subject. Advancements in 
the area such as Fourier imaging (by Kumar et al.14) and 
Echo Planar Imaging (EPI) introduced by Mansfield15 
contributed to a rapid expansion of the use of the tech-
nique in a number of contexts.

Nuclear Magnetic Resonance and Magnetic Reso-
nance Imaging and Spectroscopy have developed into 
valuable diagnostic tools during the past three decades. 
The Radiologists and the Clinicians have literally cap-
tured the technique during this period like what the 
chemists did about a half a century back. Reasons for 
such a widespread growth are built into the origin of the 
phenomenon, which involves the use of low energy elec-
tromagnetic radiation. The effects produced are, however, 
large and easily detectable with the present day technol-
ogy, leading to details of molecular structures obtained at 
the atomic level. 

APPLICATIONS OF NMR AND MRI

NMR is being used in a variety of areas. The range 
of application of NMR is illustrated in Fig.3. Leaving out 

some of the well known applications of NMR in Chem-
istry, in Bio-molecular structure determination and in 
Material Science, we highlight here applications in some 
of the other areas. 

NMR APPLICATION IN AGRICULTURE

Hydration in food stuffs: It is based on the fact that 
water molecules in many such products are more mobile 
than the protons in the host matrix. The proton spec-
tra thus consist of sharp signals superimposed on broad 
background.16

The state of absorbed water: It has been investigated 
in meat, seeds, dairy products, and vegetables.17

The effect of storage: Significant differences in the free 
and bound water on storage have been reported on pota-
toes, garlic and apples.18

Rapid distinction between oil and water in agricultural 
products: NMR has been employed in rapid distinction of 
oil and water and dedicated instruments manufactured 
for such purposes. The instrument manufacturers with 
publicity such as “…. Accurate moisture contents in SEC-
ONDS…. Not in hours” became multi-billionaires.19

Oil build-up as a function of time after flowering of 
the seeds: NMR has been used to examine the quality of 
the oil as a function of maturity of the seeds as well as 
the determination of percentages of individual saturated 
and unsaturated fatty acids in intact seeds .20

Total oil content in individual seeds: NMR has found 
extensive utility for selecting the best seeds for plant 
breeding. Such a fast and non-destructive method pro-
vides a means to increase the average oil content of 
corn 2.25 times when compared with traditional selec-
tion methods resulting in gains over five generations that 
would have otherwise taken 20-30 generations.21

Spatial distribution of water and oil in intact seeds: 
The spatial distribution of oil and water in intact ground-
nut and sunflower seeds have been obtained.22 In the 
immature commercial groundnut seeds complementary 
oil and water distributions have been observed (Fig.4). 
The two images exhibit distinctly different features indic-
ative of different intracellular environments in the two 
cotyledons – oils is present predominantly in one the cot-
yledons and water in the other. In this immature ground-
nut seed, it has been interpreted as the incomplete oil-
build up with the result that the oil and water within the 
seed are preferentially localized in complementary man-
ner. The water soluble sugars yet to be converted to stor-
age lipids are confined in one of the cotyledons. A physi-
ological disorder may be responsible for this differential 
micro environment in the two cotyledons.

Figure 3. Major applications of NMR in different areas.



29Developments of NMR - From Molecules to Human Behaviour and Beyond

SOME CLINICAL PROBLEMS INVESTIGATED USING 
NMR

The objective has been to identify specific markers for 
the quick and non-invasive diagnosis of the diseases and to 
monitor the treatment. Several problems related to human 
bile, liver graft dysfunction, Fulminant Hepatic Failure, 
bacterial urinary tract infection, mal-absorption syndrome, 
obstructive jaundice, breast disorders, congenital heart dis-
orders, benign and malignant gallbladders, alkaptonuria, 
and mitochondrial diseases have been reported.23-33 Results 
on three typical studies are briefly mentioned below. For 
details, one may refer to the cited literature.

Human Bile: Human bile being a complex mixture of 
numerous metabolites provides highly overlapping and 
complex spectra requiring the need for the highest field 
NMR especially for quantification of the individual com-
ponents. A typical 800 MHz is reproduced in Fig.5. The 

Figure 4. 1H NMR images of transverse section of a commercial 
variety of ground nut seed. Left: Water image and right: Oil image. 
The extreme right shows the scale with the concentration increasing 
from top to bottom. PERMISSION IN ATTESA

Figure 5. 1H NMR spectrum of human bile at 800 MHz. Reproduced from Ref. 26 with permission of Springer.



30 C.L. Khetrapal and K.V. Ramanathan

assignments of the resonances due to various metabolites 
are shown in the Figure. NMR in fact, provides a novel, 
unique single step method to identify and quantify such 
a large number of metabolites present in a mixture. Once 
this was achieved several problems related to Human Bile 
have been investigated.23-27

Assessment of liver graft dysfunction: A study of 
patients who underwent liver transplant was carried out. 
It was noted that some of the patients died before they 
were discharged from the hospital though surgically all 
operations appeared satisfactory. In this study, the use 
of NMR has been made to find out the reason for the 
death. Studies on serum and urine samples of patients 
before liver transplantation and every 24 hours after the 
liver transplantation, till the time they were discharged/
alive, were taken. High levels of glutamine in both serum 
and urine and concomitant reduced urea levels in urine 
were found to be evidence of impairment in urea cycles 
and compatible with abnormal graft function. Increased 
glutamine levels lead to brain death, if untreated. This is 
medically useful information since it gives prior informa-
tion on what is going to happen and one may take cor-
rective measures in advance.28

Prediction of therapeutic outcome in patients with 
Fulminant Hepatic Failure: Fulminant Hepatic Failures 
(FHF) are associated with severe liver injuries leading 
to impairment of hepatic function followed by hepatic 
encephalopathy within eight weeks of the onset of the 

illness. The mortality rate is as high as 80%. Liver trans-
plant for FHF patient appears to be the only effective 
answer to this. Since the survival rates are low, rapid 
diagnosis is necessary to identify patients for trans-
plantation. Until today, there is no means to predict the 
spontaneous recovery or non-recovery for such patients. 
1H NMR to quickly identify molecular markers such as 
glutamine in serum and urine and urea in urine prom-
ise a potential in quickly deciding on liver transplanta-
tion. NMR spectroscopy has been used to determine the 
molecular markers in serum and urine to distinguish 
between those recovered patients and those who did not. 
Glutamine in serum and urine glutamine/Creatinine 
ratios were higher in non-surviving patients compared 
with surviving patients. On the other hand, no significant 
differences were found in conventionally employed clini-
cal parameters such as serum alanyl-amino transferase, 
aspartyl-aminotransferase and bilirubin.29

Bacterial urinary tract infection: Qualitative and 
quantitative estimations of metabolites produced as a 
result of bacterial infection in the urinary tract have been 
reported. Absolute concentrations of the metabolites pro-
vide the severity of the infection and, are likely to be very 
valuable in patients on antibiotic therapy with negative 
urine cultures.Major bacteria in UTI are E.coli, K. penu-
moniae, P. aeruginods and P. mirabilis. They uniquely 
metabolize lactose to lactate, glycerol to 1, 3- propan-
ediol, nicotinic acid to 6 hydroxy nicotinic and methio-

Figure 6. Distinction between real bacterial infection and contamination. Reproduced from Ref. 31 with permission from John Wiley & 
Sons, Inc.



31Developments of NMR - From Molecules to Human Behaviour and Beyond

nine to 4-methyl-oxobutyric acid, respectively.30-33 These 
properties have been exploited to identify and quantify 
specific bacteria responsible for the infections. The NMR 
technique has also been employed to distinguish between 
the real infection and contamination as shown in Fig.6. 
This is in fact one of the major problems in the precise 
diagnosis of UTI and NMR provides a solution.

EXAMPLES OF APPLICATIONS OF MRI

MRI is especially valuable for detailed imaging of 
the brain and the spinal cord. Nearly all brain disorders 
lead to alterations in water content, which is reflected 
in the MRI picture. A difference in water content of less 
than a percent is enough to detect a pathological change. 
In multiple sclerosis, examination with MRI is superior 
for diagnosis and follow-up of the disease.34 The symp-
toms associated with multiple sclerosis are caused by 
local inflammation in the brain and the spinal cord. With 
MRI, it is possible to see the of the inflammation in the 
nervous system and how intense it is, and also how it is 
influenced by treatment. MRI is an important preopera-
tive, improved diagnostic and reduced suffering tool for 
patients.

MRI has been used to reveal the effects of YOGA 
on brain. The results show that concentration of Gam-
ma Amino Butyric Acid (GABA), increases by perform-
ing certain YOGA exercises.35 It implies that YOGA, and 
perhaps some other forms of exercise should be utilized 
as a complementary treatment for depression and anxi-
ety disorders. The results have clear public health utility. 
Yoga should be compared with other forms of exercise to 
determine whether or not it is the nature of YOGA pos-
tures that results in raised GABA levels, or it is an effect 
of any exercise. 

FUNCTIONAL MRI (fMRI)

Functional MRI is based on the fact that oxyhemo-
globin is diamagnetic but when oxygen is consumed in 
metabolism, the haemoglobin becomes paramagnetic. 
This permits visualization of the regions of the brain in 
which metabolic activity occurs in response to an exter-
nal stimulus.36 It can characterize functions while brain 
processes thoughts, sensations, memories, and motor 
commands. Functional MRI makes it possible for neu-
rologists to detect early signs of Alzheimer’s disease and 
other disorders, to evaluate drug treatments, and pin-
point tissue housing critical abilities like speech before 
venturing into a patient’s brain with a scalpel. Such 

results provide a basis for designing new intervention 
techniques.

ILLUSTRATIVE APPLICATIONS OF fMRI

Considering the importance of the subject and its 
direct societal relevance, numerous interdisciplinary 
groups and institutions in this field have been established 
all over the world during the past few years. Basic and 
social scientists, psychologists and medical doctors are 
now joining hands to exploit the interdisciplinary nature 
of the field in order to diagnose and understand not only 
the molecular structure and the diseases in human beings 
but also to understand the metabolic and structural 
changes in them. Some illustrative applications are briefly 
described below:

The dyslexics and non-dyslexics: Numerous groups 
all over the world are involved in investigating biologi-
cal bases of learning and learning disorders essentially 
because of great societal need. It has been reported that 
the deficiencies in functional brain organization under-
lying dyslexia can be reversed after sufficiently intense 
intervention lasting as little as 2 months. The reading dif-
ficulties in many children represent a variation of normal 
development that can be altered by intensive interven-
tion.37 Such investigations are of great importance.Imme-
diate creation of an interdisciplinary school on child psy-
chiatry, social science and fMRI is the need of the hour 
in societal interest.

Alcoholism in young adult, female alcoholics: Specific 
areas of the brain impaired by years of heavy drinking 
have been identified in young adult women. Previously, 
investigators have relied on thinking and memory tests 
to gauge brain dysfunction in alcoholics, but no one had 
identified the actual brain sites where impairment occurs 
in young adults. Even young and physically healthy indi-
viduals risk damaging their brains through chronic, 
heavy use of alcohol.38

Pretty female faces: They trigger activity in men’s 
brains. A beautiful woman’s face is like chocolate, cash or 
cocaine to a young man’s brain.39 When men in the study 
were shown pictures of various faces, only the female 
faces deemed beautiful triggered activity in brain regions 
previously associated with food, drugs and money. 

Sex differences in mental rotation and spatial working 
memory: Behavioural and neural sex differences in sex-
specific spatial abilities have been investigated.40 Males 
typically surpass females on tasks dealing with men-
tal rotation and spatial navigation, while females tend to 
excel males on tasks dealing with object location, relation-
al object location memory or spatial working memory.



32 C.L. Khetrapal and K.V. Ramanathan

Crime and lie detection: During the past few years, 
the data on crime detection by NMR has become volu-
minous. Several hundred thousand entries are found in 
‘Google search’ under this category. Pathological liars 
have been found to have brain abnormalities. Brain 
deformities have been observed in people who habitu-
ally lie, cheat and manipulate. The brain area just behind 
the forehead exhibits structural difference among patho-
logical liars41 and their white matter content is more. The 
finding could be used in making clinical diagnosis and 
may find applications in daily life, criminal justice system 
and the business world. The fMRI is bound to transform 
the societal values system, the security and the judicial 
processes. By mapping the neural circuit behind decep-
tion, fMRI will provide a new kind of ‘lie detector’ that 
is more probing and accurate than the polygraph – the 
standard lie-detection tool being employed for nearly 
a century. fMRI may change the entire judicial system. 
It will be useful in high-profile crimes like terrorism. It 
may appear that fMRI is expensive, bulky, noisy and time 
consuming for such routine applications. However, if one 
thinks of the cost of judicial process taking years to dis-
cover the truth or the price of missing a terrorist, nations 
can certainly afford it as far as the present costs are con-
cerned. With more advances in technology, many of the 
limitations may be overcome as discussed in the subse-
quent sections.

Enhancement of trust among humans: Intranasal 
administration of oxytocin, a neuropeptide causes a 
substantial increase in trust among humans.42 Oxytocin 
specifically affects an individual’s willingness to accept 

social risks arising through interpersonal interactions. An 
fMRI study may throw light on Biological basis and pro-
vide scientific evidence on the role of oxytocin or human 
behaviour.Most charitable people show enhanced activ-
ity in the top and back of the brain – an area normally 
linked to processing incoming information, sorting out 
social relationships and controlling movements! Under-
standing the function of this region may give clues on the 
origin of social behavior.43

Science behind health benefits of YOGA and medita-
tion: Though it is well known that YOGA and MEDITA-
TION can reduce stress and cure many diseases, recent 
times have seen the emergence of scientific evidence to 
demonstrate these beneficial effects using modern scien-
tific technologies such as fMRI. These results are draw-
ing worldwide attention. Neuro-imaging and genomics 
technology have been employed to measure physiological 
changes in greater detail. Some typical studies are out-
lined below:

fMRI study of neuro-cognitive effect of sound “OM” on 
human Brain: The sound “OM” is of paramount impor-
tance and is supposed to relax human beings physically, 
mentally and emotionally. The fMRI results delineate the 
exact brain area involved in response to OM sound and 
reveal that listening OM recruits areas of both left and 
right hemispheres including left prefrontal cortex. This 
corresponds to “OM” as a pleasant melodic sound which 
increases attention and emotional quotient and creates 
intuitive feeling towards spirituality (Fig. 7). Such stud-
ies provide a unique idea to employ modern scientific 
technologies to demonstrate whether YOGA pertains to a 

Figure 7. Neuro-cognitive effect of “OM” sound. (Supplementary Motor Area (SMA):Involved in MotorcoordinationSuperior tempo-
ral gyrus (STG): Auditory perceptionInferior frontal gyrus (IFG): Perception of pleasant soundDorso-lateral pre-frontal cortex (DLPC): 
involved in monitoring of attention process.)



33Developments of NMR - From Molecules to Human Behaviour and Beyond

particular faith or religion or it is universal. It may go a 
long way to establish religious harmony and world peace 
if such an idea is pursued. The observation of the inter-
national YOGA day has generated hot debates particu-
larly in India on whether YOGA pertains to a particular 
religion or faith. The use of modern scientific technolo-
gies such as functional MRI and other technologies can 
throw light on the issue in an unbiased manner and 
will go a long way to establish world peace and happi-
ness and religious harmony. The functional MRI studies 
reported above delineate the exact brain areas involved in 
response to OM sound and reveal that listening to OM 
sound recruits areas in the brain involved in increas-
ing attention and emotional quotient and creates intui-
tive feelings of happiness.44-47 A question arises whether 
such studies can result in providing a scientific approach 
to achieve religious harmony and world peace? It would 
be interesting to see whether ‘OM’ is faith specific or it 
affects similarly to all irrespective of the religion or faith. 
One could even study the effects of “Mantras” preached 
by different religions. If all have similar effects, it will 
establish scientifically for the first time that all religions 
preach the same thing and if the effects are specific only 
to OM, then it will establish that this sound is universal 
and is independent of the religion. If studies of the Man-
tras preached by different religions demonstrate changes 
in different areas of the brain but they too have positive 

health benefits it will throw a challenge to scientists to 
discover a “universal Mantra” which takes into accounts 
positive aspects of all faiths. The results will establish a 
correlation between spirituality and science.

“SOHAM” Meditation: The parts of the brain that 
show activity during meditation in general in fMRI is 
illustrated in Fig. 8. In “SOHAM” meditation one merely 
observes the breathing process even as one repeats the 
word  ”SOHAM” in mind,  synchronising it with breath. 
Therefore the process is when one inhales, one mentally 
repeats the sound “SO” and while exhaling the sound 
“HAM” is repeated. As one breathes in and out the 
sound “SOHAM” is repeated. Grey Matter in the brain 
fills about 40 percent of the whole brain in humans and 
consumes 94 percent of oxygen. The senses of the body 
(speech, hearing, feelings, seeing and memory) and con-
trol of the muscles, are part of the grey matter’s functions. 

Differences in Grey Matter are observed between 
“SOHAM” meditators and non-meditators (Fig. 9). Three 
distinct regions show higher grey matter concentration in 
meditators .

Positive attitude insures happiness: The power of posi-
tive attitude or perception, meditation, reciting and lis-
tening mantras etc in coping up of the various stresses 
and strains in human daily life is well known and is wide-
ly practiced. However, it may have better impact on com-
mon man’s daily life if one can demonstrate this by a sci-

Figure 8. Effect of SOHAM Meditation on the brain. Middle frontal cortex (MFC): This implies regulation of attention, which in the case 
of meditation is directed at the subjects own mental and bodily state.Left Inferior frontal gyrus (IFG): involved in the cognitive aspects of 
emotional processing , such as paying attention to emotion or the identification of emotion.Precuneus: involved in the execution or prepara-
tion of spatially guided behaviors. Reprinted from Ref. 45, Copyright 2013, with permission from Elsevier.



34 C.L. Khetrapal and K.V. Ramanathan

entific evidence. A preliminary fMRI study (Brain imag-
ing and behavior, August 2012) demonstrates that nega-
tivity is perceived by different brain regions compared 
to positive perception. The experiments decode specific 
regions in human brain involved in positive and nega-
tive perceptions. A crucial finding was the activation of 
the bilateral temporal pole for negative sentences (indi-
cating sadness, anxiety and stress). No such effects were 
observed in affirmative sentences (Fig. 10). A study48 on 
mentally depressed and anxious individuals also shows 
activation pattern similar to that in subjects with negative 
thoughts (Fig. 11). 

RECENT ADVANCES IN NMR, MRI AND FMRI 
TECHNOLOGY

Nano particles and fMRI: The new generation of 
nanoscale calcium contrast agents being developed will 
have applications in understanding learning, memory, 
and behaviour and will allow functional fMRI to make 
transition from imaging gross properties of brain to a 
fine-tunes analysis based on information flow involving 
cells and circuits .49

A new low-cost, portable MRI technology: A novel 
laser-based MRI technique is being developed by the 
Alex Pines and his colleagues in Berkeley. It provides a 
viable alternative for MRI detection with substantially 
enhanced sensitivity and time resolution. It will result 
in the development of a low cost, compact, portable and 
battery-powered portable MRI technology and an on-line 
analytical instrument for monitoring chemical reactions 
and biological processes.50

NMR: From K gm to Pico gm: The quantity of the 
paraffin sample initially used by Purcell when he discov-
ered NMR in bulk material was 1 K gm in weight and 
with developments or organic molecules possessing elec-
tronic properties analogous to those of Gallium Arsenide, 
it seems likely that NMR spectra of Pico gm quantities of 
Proteins and Nucleic acids could be recorded.51

NMR nanometer-scale device: NMR has received 
considerable attention in the context of quantum com-
putation and information processing which require con-
trolled coherent qubit operations. Towards achieving 
this goal, a self-contained NMR semiconductor device 
has been implemented that can control nuclear spins in 
a nanometre-scale region. High sensitivity at the micro-
scopic level has been demonstrated for probing materials 
whose nuclei contain multiple spin levels and thus form 
the basis of a versatile multiple qubit device.52 

NMR on a chip: If a Nanoscale gallium Arsenide 
structure is excited with an oscillating Magnetic Field, 

Figure 9. Grey Matter differences in “SOHAM” meditators and 
non-meditators: Three distinct regions show higher grey matter 
concentration in meditators. Left Image: Brain stem - Regulates 
breathing and anxiety level. Right Image:Ventral palladium- Regu-
lates positive mood and motivation. Bottom Bottom:Motor area - 
Regulates motor aspects.

Figure 10. Influence of negation on Human Brain. Distinct neural 
regions for negative sentences: Temporal Pole: This region is associ-
ated with anxiety and depression.

Figure 11. Brain activation (bright color) characterizing the func-
tioning of anxious and depressed persons as they Process emotional 
information and respond to various types of positive and negative 
stimuli. Reproduced with permission of the Stanford Mood and 
Anxiety Disorder Laboratory.



35Developments of NMR - From Molecules to Human Behaviour and Beyond

superposition of nuclear spin states can be created and 
detected electrically. Quantum computing could be the 
beneficiary.51

CONCLUSIONS

To the question “Is there an end in sight for the new 
exciting developments in NMR?”, the answer is a simple 
“NO”. If one just looks at the advances in technology and 
the possible applications outlined above, one may pre-
dict that the best is yet to come. If a young man wants 
to remain “young”, here is an opportunity to enter the 
“young” field and get assured enjoyment and excitement 
for the rest of the life.

ACKNOWLEDGEMENT

K V Ramanathan would like to thank the Council of 
Scientific and Industrial Research, India for the grant of 
an Emeritus Scientist position to him. The authors would 
like to thank Prof. Anil Kumar for a careful reading of 
the manuscript and for his comments.

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