Functional neuroimaging in psychiatry

1. Functional Neuro-Imaging
in Psychiatry
1
Presenter: Dr. Amit Chail, Resident (Psychiatry)
Moderator: Dr. K Chatterjee, Professor (Psychiatry)

2. Overview
• Aim
• Introduction
• History
• Functional Imaging Techniques
• Physics and principles
• Applications in Psychiatry
• Future trends
• Take home message
• References
2

3. Aim
• Familiarisation to functional Neuro-imaging modalities
• fMRI / MRS / DTI/ SPECT / PET
•Physics & Techniques
•Interpretation
• Relevance to psychiatry
• Current
• Future
3

4. Introduction
• Prospective method
• Structural & Functional correlates of
– Psychiatric disorders
– Psychopathology (Perception/ thought/
Behavior)
– Diagnosis / Prognosis / Taxonomy
– Where do I hit ??
– Do I cure? Can I?
– Organicity in Functional disorders
4

5. Classification of Neuro-imaging Techniques
X Ray Skull
radiography,
CT Scan
NMR MRI, fMRI,
MRS, DWI,
MRA
Emission PET ,
SPECT
5
Structural Plain skull
XRay,
PEG,
CT Scan,
MRI
Functional fMRI
MRS
SPECT
PET
DWI/DTI

6. Structural Neuro-Imaging- Background
Alzheimer’s
Dementia
MTL atrophy -marker - MCI
Whole-brain and hippocampal atrophy rates -
markers of progression of neurodegeneration
Schizophrenia •Total Brain Vol, GM loss > WM
•Increased ventricular size/ CSF Vol,
•30% lower reductions in antipsychotic-naïve
compared with the medicated patients
•Progressive volume decreases for frontal,
temporal, and parietal white matter
Depression Decrease in right hippocampal volume-
poorer treatment response
6
P. Fusar-Poli, A meta-analysis of longitudinal MRI studies, Neuroscience and Biobehavioral
Reviews (2013)

7. Structural Neuro-Imaging- Background
ADHD Reduced right globus pallidus and putamen volumes
as well as decreased bilateral caudate volumes
Adults - ADHD symptoms - (ACC) volume reduction
OCD Reduced GM volume - inferior and medial frontal
gyrus, cingulate gyrus, superior temporal gyrus, and
insula and caudate nucleus
PTSD Reduced Hippocampal (B/L), ACC and Left Amygdala
BPAD •Reduced volume- OFC, DLPFC, left precentral gyrus
Hippocampal GM & amygdala
•Increase –B/L amygdala, left hippocampus and
bilateral thalamus in lithium-treated
7
Carlos López-Jaramillo, Increased hippocampal, thalamus and amygdala volume in long-term
lithium-treated bipolar I disorder patients compared with unmedicated patients and healthy
subjects, Bipolar Disorders 2017

8. History of Neuro-imaging
8
MRI Handbook: MR Physics, Patient Positioning, and Protocols, M. Elmaoğlu, First Edn,
2012 Springer Science+Business Media
Wilhelm K Roentgen,
Discovery of X Ray, 1895
Nobel Prize, Physics, 1901
Godfrey Hounsfield,
CT Scanner, 1972
Nobel Prize, Medicine, 1979

9. History of Neuro-imaging
9
MRI Handbook: MR Physics, Patient Positioning, and Protocols, M. Elmaoğlu and A.
Çelik, Springer Science+Business Media, LLC 2012
Discovery of NMR,1946
Nobel Prize, Physics,
1952
Richard Ernst
Fourier
transformation,
1964
Nobel Prize,
Chemistry, 1991
Human MR images, 1970s
Nobel Prize, Medicine 2003

10. MRS
10

11. 11
1975 – PET scanner
Seiji Ogawa & Kenneth Kwong

12. NMR- Basic Physics
12

13. Liquid Helium Cooled
Solenoid Magnet
Patient Platform
Radiofrequency
Transmitter/ Receiver Coil
13

14. Contd….
14

15. Basic Concepts/ Physics of MR
• NMR:
– MRI & MRS
• Spin of certain (odd) nuclei
can be detected after
magnetisation
– Species of nucleus
– Strength of Magnetic Field
• Detection of net
magnetisation
10
MRI Handbook: MR Physics, Patient Positioning, and Protocols, M. Elmaoğlu and A.
Çelik, Springer Science+Business Media, LLC 2012

16. 16
RF pulse
External Magnetic Fd
MRI Handbook: MR Physics, Patient Positioning, and Protocols, M. Elmaoğlu and A.
Çelik, Springer Science+Business Media, LLC 2012

17. The Magnetization Vector
17
Kaplan and Saddock’s Comprehensive Textbook of psychiatry, 9th edn, 2009 LWW

18. Image Convention
19
Neuroradiology- The Prerequisites – 3rd edn, Grossman, 2010

19. MR Spectroscopy (MRS)
20

20. MR Spectroscopy (MRS)
• Non invasive in-vivo
chemical assay
• Information in form of
a spectrum
• Biochemical
information
contained within a
selected voxel of
tissue
• Nuclei used in
psychiatric
research-
– 1H, 31 P
21
Ai-qin Lin, Metabolic changes in acute cerebral infarction: Findings from proton Magnetic
Resonance Spectroscopic imaging, Experimental And Therapeutic Medicine, 2013

21. 22
Baló's concentric sclerosis presenting as a stroke-like syndrome, Ellen M Mowry,
John H Woo and Beau M Ances, Nature Clinical Practice Neurology (2007) 3, 349-
354doi:10.1038/ncpneuro0522

22. Nuclei Uses in MRS
H¹ Amino acid neurotransmitters and neuronal
and glial compounds; imaging of water and
lipids
C¹³ Study of metabolic pathways
P³¹ High energy phosphate levels, intracellular
pH, phospholipid head groups
Li 7 Pharmacokinetics of lithium
O 15 Cerebral O2 consumption
F 19 Cerebral pharmacokinetics of fluorinated
drugs like fluoxetine and fluvoxamine
23
Maddock R, MR Spectroscopic Studies of the Brain in Psychiatric Disorders, Curr Topics
Behav Neurosci, Springer-Verlag Berlin Heidelberg 2012

23. H¹ 2 ppm – NAA Neuronal Health, viability and
mitochondrial function
3.2 ppm - Cho
peak
Reflect membrane turnover
In pathological process like
gliosis Cho peak -elevated
1.3 ppm –
Lactate
Cerebral Lactate is elevated in
ischemia, hypoxia or in tumors
3.5 ppm –
Inositol
metabolites
Intracellular msg transduction
Serves as glial cell marker and
indicator of neurotoxicity
24
Lin A, Metabolic changes in acute cerebral infarction: Findings from proton magnetic
resonance spectroscopic imaging, Experimental And Therapeutic Medicine, 2013
Maddock R, MR Spectroscopic Studies of the Brain in Psychiatric Disorders, Curr Topics
Behav Neurosci, Springer-Verlag Berlin Heidelberg 2012

24. Dementia NAA & MI Neuronal loss & Gliosis
MRS & Psychiatry
Mood
disorders
Li-7 & F-19 Pk & Brain conc of drugs
H-1 NAA Hippocampus (depressed/anxious)
Frontal (Bipolar)
H-1 choline Basal Ganglia
H-1 GLX Reversible GABA & glutamate/
glutamine level abnormalities
P-31 PME BPAD; dys-regulated signal
transduction and membrane
metabolism.
25
Maddock R, MR Spectroscopic Studies of the Brain in Psychiatric Disorders, Curr Topics
Behav Neurosci, Springer-Verlag Berlin Heidelberg 2012

25. NAA Cortical and limbic areas
MRS & Psychiatry- Schizophrenia
26
MRS finding Meaning PM correlate Other Evidence
NAA –
medication
naïve.
Impaired
neuronal
integrity
(structural)
neuronal
size and
dendritic
arborization
DTI – disturbed
integrity of
long fiber
pathways
metabolic
disturbances
Mitochondrial
dysfunction
PET
Glutamate
I Glutamine
Over activity of Glu transmission
Maddock R, MR Spectroscopic Studies of the Brain in Psychiatric Disorders, Curr Topics
Behav Neurosci, Springer-Verlag Berlin Heidelberg 2012

26. MRS & Psychiatry
ADS H-1 NAA Alcohol related neuro-toxicity
H-1 choline
H-1 GABA N- acute withdrawal
- Recovery/ Abstinence
27
Maddock R, MR Spectroscopic Studies of the Brain in Psychiatric Disorders, Curr Topics
Behav Neurosci, Springer-Verlag Berlin Heidelberg 2012

27. Current Trends MRS
• Correlation of metabolites (Glx) with symptoms and
role of intervention
– Elevated Glx in certain brain areas in Schizophrenia
– H1 MRS
– Anti-psychotic treatment lowers Glx
– Corresponds with symptoms reduction in some of
the studies
• BPRS
• PANSS SANS
28
Egerton A, Effects of Antipsychotic Administration on Brain Glutamate in Schizophrenia
A Systematic Review of Longitudinal 1H-MRS Studies. Front. Psychiatry, (May 2017)

28. Functional MRI (fMRI)
29

29. Functional MRI (fMRI)
• Principle: differential magnetic
susceptibilities of O2-Hb and
deoxygenated Hb
• Differential r CBF & r CMR
• DeOxy-Hb is para-magnetic
• Oxy Hb is diamagnetic
• Lower the de-oxy Hb  better
the signal from the adjacent
tissue. i.e images are BOLD
• Detect tissue perfusion not the
neuronal metabolism
30
Clinical Applications of Functional MRI, Neuroimaging Clinics of North America, Nov 2014

30. Mechanism of BOLD fMRI
Brain activity
Oxygen consumption Cerebral blood flow
Oxyhemoglobin
Deoxyhemoglobin
Magnetic susceptibility
T2*
MR signal intensity
31
Clinical Applications of Functional MRI, Neuroimaging Clinics of North America, Nov 2014

31. Functional MRI (fMRI)
32
Silvia Francesca Storti, Automatic selection of resting-state networks with functional
magnetic resonance imaging , Front. Neurosci., 20 May 2013

32. 33
Kaplan and Saddock’s Comprehensive Textbook of psychiatry, 9th edn, 2009 LWW

33. fMRI
• Indications
• Role in seizure localisation
• Study of neurodevelopmental disorders
• Post-stroke recovery
• Limitations
– Vascular pathology reducing regional blood
flow will impede signal acquisition by BOLD
imaging
– Psychotropic drugs
• BZD agonist , antipsychotics – reduce CBF
34
Clinical Applications of Functional MRI, Neuroimaging Clinics of North America, Nov 2014

34. fMRI & Psychiatry
35
Gur et al , FMRI in schizophrenia , Dialogues in Clinical Neuroscience - Vol 12 . 2010

35. fMRI & Psychiatry
36
Iwabuchia SJ, Localized connectivity in depression: A meta-analysis of resting state
functional imaging studies , Neuroscience and Biobehavioral Reviews 51 (2015)

36. fMRI & Psychiatry
37
Dementia Schizophrenia Mood Disorders
Serial fMRI-
differential rate of
volume changes
Alterations in
fn connectivity
LTC
LCSPTC
Reduced activation
of MTL
Activation of
PFC
rCBF & rCMR
in OFC & VLPFC
No diagnostic
criteria
rCBF & rCMR
in DLPFC
ReHo in MPFC
Iwabuchia SJ, Localized connectivity in depression: A meta-analysis of resting state
functional imaging studies, Neuroscience and Biobehavioral Reviews 51 (2015) 77–86

37. fMRI in Substance Abuse
• GM volume reduction in ADS - frontal and temporal
lobes
• Heavy drinking is associated with greater volume
loss
• Abstinent demonstrated greater tissue gain than LD
or relapse.
• Recovery in GM > WM.
38
Valerie A. Cardenas, Deformation-based morphometry of brain changes in alcohol
dependence and abstinence, NeuroImage 34 (2007) 879–887

38. fMRI in Substance Abuse- Stimulant
– Compromised white matter integrity
– leading to functional impairments in decision
making.
39
Karen D Ersche, Meta-analysis of structural brain abnormalities associated with stimulant
drug dependence and neuroimaging of addiction vulnerability and resilience, Current
Opinion in Neurobiology 2013,

39. fMRI Impact
40
Cognitive
neuroscience
Affect/ emotion
Reward pathways- neuro-economics
Memory
Default mode network
Plasticity and brain development
Legal Minimum age for capital punishment
Lie detector
Neuro-imaging before capital punishment
Social: Parity
Insurance
Social cognition & meta-cognition (MFC)
Therapeutic Reversibility of rCBF changes in depression
Compliance
Efficacy of treatments like DBS

40. Diffusion MRI
41

41. Diffusion MRI
• Principle: diffusion of
water molecules provides
contrast
• Information about the
integrity and orientation
of white matter tracts in
the brain.
• Assessing the tract
disruption in disease
states
42
Mori S, Principles of Diffusion Tensor Imaging and Its Applications to Basic Neuroscience
Research, Neuron, Volume 51, Issue 5, 7 September 2006

42. Diffusion MRI
• Clinical utility:
• Early identification
of ischemic stroke
• Differentiation of
acute from chronic
stroke
• Assessment of the
extent of diffuse
axonal injury
• Assessment of
active demyelination
43
Mori S, Principles of Diffusion Tensor Imaging and Its Applications to Basic Neuroscience
Research, Neuron, Volume 51, Issue 5, 7 September 2006

43. • Diffusion Tensor
Imaging (DTI)
–Type of DWI
–several sets of
diffusion weighted
images are acquired
with the diffusion
gradients applied in
different directions.
–Enables the
detection of diffusion
anisotropy in various
mediums such as brain
white matter.
44
Mori S, Principles of Diffusion Tensor Imaging and Its Applications to Basic Neuroscience
Research, Neuron, Volume 51, Issue 5, 7 September 2006
Han-Cheng Wang , Diffusion Tensor Imaging of Vascular Parkinsonism, Arch neurol/vol 69

44. 45
Shizukuishu T, Diffusion Tensor Imaging Analysis for Psychiatric Disorders; Systematic Review,
Magn Reson Med Sci, Vol 12, 2013

45. 46
DTI & Alzheimer's Disease

46. 47
Radio tracer Imaging

47. Radio tracer Imaging
• Radio – unstable atom that decay
• Tracer – administered in trace amounts
• Typical tracer methods
– PET
– SPECT
• PET – positron emitter – collides with electron - two
photons released
• SPECT – decays – single high energy photon
48

48. Radio tracer Imaging (Contd.)
• Process of interest –
– incorporate radionuclide
in to a molecule of
known
physiological significance.
• RADIOTRACER
– Inhalation
– Ingestion
– Intravenous
• Tracer uptake measured
over time PET
49

49. COINCIDENCE
CIRCUIT
ANNHILATION
50

50. PET SPECT
Radiotracer 18F- FDG
C-13 or O-15
Xe-133, Tc-99
Physics Annihilation 
Gamma emission
Direct Gamma
photon emission
Principle Co-incidence
detection
Back Projection
Spatial
resolution
2-5 mm 7-10 mm
Measures rCBF & rCMR rCBF & rCMR
51

51. 52
Kaplan and Saddock’s Comprehensive Textbook of psychiatry, 9th edn, 2009 LWW

52. PET IN COGNITIVE IMPAIRMENT
53

53. Mood Disorders
• PET
– Hypofrontality on frontal lobe in MDD but reversal
occurs in Mania.
– Less 5HT Tpt (SERT) availability in MDD
– More 5HT 1A predict poor response.
– High DAT availability in Rt caudate in MDD
– Increased ACC and OFC activity - positive response
to treatment
– Activation in the right amygdala, striatum and
insula -poor response
54
Cynthia H.Y. Fu, Predictive neural biomarkers of clinical response in depression:
A meta-analysis of functional and structural neuroimaging studies of pharmacological and
psychological therapies, Neurobiology of Disease 52 (2013) 75–83

54. PET in Depression
56
Cynthia H.Y. Fu, Predictive neural biomarkers of clinical response in depression: A
meta-analysis of functional and structural neuroimaging studies of pharmacological
and psychological therapies, Neurobiology of Disease 52 (2013) 75–83

55. Substance Abuse
• PET & SPECT-
– Deficit DA in mesolimbic system
– Low 5HT in Type B & reverse in Type A
– GABA receptor levels are low in frontal, temporal
and parietal cortices in dependent cases.
– HMPAO SPECT – poor rCBF in WKS
– In Cocaine dependent -hypodopaminergic state &
high DAT levels.
57
Kaplan and Saddock’s Comprehensive Textbook of psychiatry, 9th edn, 2009 LWW

56. Future Directions
• Simultaneous PET/MRI
– Biomarkers for
psychiatric disorders
• DTI
– Tracts for identification
of various pathologies.
• Genetic-Imaging studies-
predicting vulnerabilities
• The future of fMRI lies in
understanding the
pathophysiology, diagnosis
and prognosis of Psychiatric
disorders (Thomas Insel) 58

57. Magnetoencephalography
59
Sanjay P. Singh, Magnetoencephalography: Basic principles, Ann Indian Acad
Neurol. 2014 Mar;

58. Take Home Message
60
• Neuro-imaging provides a valuable and reliable tool in
delineating organicity
• Functional neuro-imaging can demonstrate subtle
physiological changes before the actual structural
changes become evident
• Concept of organic and functional disorders
• Physiological correlates of Psychiatric disorders have
been shown
• ? Causal / Vulnerability
• Cost and availability- restrict their use as universal
diagnostic biomarkers

59. References
• Kaplan and Saddock’s Comprehensive Textbook of
psychiatry, 9th edn, 2009 LWW.
• New Oxford Textbook of Psychiatry, 2nd edn, 2012, OUP
• Kaplan and Sadock's Synopsis of Psychiatry 11th
Edition, 2014, LWW
• Neuroradiology- The Prerequisites – 3rd edn, Grossman,
2010
• Clinical Applications of Functional MRI, Neuroimaging
Clinics of North America, Nov 2014
61

60. THANK YOU
62