2009/11/10 morning meeting reporter r2 黃莉婷 supervisor 鄧復旦 主任
TRANSCRIPT
2009/11/10
Morning Meeting
Reporter R2 黃莉婷Supervisor 鄧復旦 主任
J Psychiatry Neurosci 2004;29(4):268-79
Introduction
• Major depression
>> 13% in men, 21% in women
>> Refractory to drug treatmen: 30%
Electroconvulsive therapy (ECT) Repetitive transcranial magnetic stimulation (rTMS)
Topics
• Symptoms and cognition in major depression
• Neuroimaging studies of depression
• rTMS as treatment for depression
• Structure and function of the MDLFC and the ACC
• Combined TMS / positron emission tomography (P
ET) studies of frontocortical connectivity
Symptoms and cognition in major depression
• Depressed mood• Decreased drive and motivation
• Impaired cognitive performance
in learning,memory, attention,
executive, motor, perceptual functions.
• Impairement to resist interference or initiate actions.
Neuroimaging studies of depression
Left middorsolateral frontal cortex (MDLFC) Hypometabolism and hypoperfusion correlated with severity of depression
Neuroimaging studies of depression
Anterior cingulate cortex (ACC)
increased metabolic activity
Antidepressant treatment : neural activity ↓
Neuroimaging studies of depression
• The involvement of the MDLFC / ACC in depression• The reversibility of depression-related “abnormalities
Transcranial Magnetic Stimulation (TMS)
• Stimulate specific cortical regions of the brain changes in behaviour
• Apply in trains of pulses: repetitive TMS or rTMS
rTMS as treatment for depression
• Left MDLFC
>> 5 cm anterior to the primary motor cortex (M1)• High-frequency stimulation (> 1 Hz) • 10 daily session• The mean before-versus-after decrease in the
Hamilton Depression Rating Scale (HDRS) scores
34% (range 15%–62%)
The Avery-George-Holtzheimer database of rTMS depression studies.
Active rTMS was superior in producing clinical response number-needed-to-treat : 6
Structure of the MDLFC
• The middle frontal and superior frontal gyri
areas 46 and 9/46 (middle frontal gyrus)
area 9 (superior frontal gyrus)
Connections of the MDLFC
• Bidirectional with post. neocortical areas:
visual (prestriate and inferior temporal cortices)
auditory (superior temporal cortex)
somatosensory (parietal cortex)• Reciprocal with the ant.and post. cingulate cortices
Function of the MDLFC
>> Organize and plan sequences of responses
>> Select appropriate strategies
>> Monitor self-generated actions
• Motor planning, organization
• Integration of sensory and mnemonic information
• Regulation of intellectual function and action
• Working memory
Structure of the ACC: heterogeneous
Function of the ACC: heterogeneous
Cognitive Visceral
Area 24 and 32 25
Location supracallosal subcallosal
Connection MDLFC The post. orbitofrontal areaHypothalamus,Ventral striatum, Periaqueductal grey
Function of supracallosal ACC
• Volitional control of behaviour
• Characteristics of speech production during sad affect
• Bilateral cingulate lesions
akinetic mutism monotonous intonation
a low frequency of spontaneous utterances
Combined TMS/PET studies to
assess both potential mechanisms
Possible neural mechanisms of rTMS
• Modulate activity in the specific neural circuits
that mediate a given group of symptoms
• Facilitation of monoaminergic neurotransmission
The first type of study
• The corticocortical connectivity of the MDLF
and its modulation by brief periods of rTMS
• PET ligands 15O-H2O
> regional distribution of cerebral blood flow (CBF)
>> the amount of excitatory neurotransmission
Method
Corticalconnectivity of the left MDLFC
modulatory effectof rTMS
After doublepulse TMS …
• CBF decreased both at the stimulation site and in several distal regions, including the ACC
• TMS γ-aminobutyric acid (GABA) release
a net decrease in excitatory synaptic activity
Following the 2 series of rTMS …
“Suppression” response was reversed
increases in cerebral blood flow (CBF)
Regression analyses
The blood-flow response to double-pulse TMS covaried with that at the stimulation site, including the contralateral MDLFC and the ACC
Summary
• Low-frequency TMS inhibitory response • rTMS cortical excitability and connectivity ↑• “Long-term transformation”
GABA mediated inhibitory postsynaptic potentials
Depolarizing responses
The second type of study
• TMS-induced release of dopamine
• PET ligands : 11Craclopride
>> regional dopamine concentration
Method
• 15 10-Hz trains of rTMS * 3 series * 2 day
• The left MDLFC / the left occipital cortex
Measure regional release of dopamine
rTMS over the left MDLFC
Left caudate nucleus
11C-raclopride binding potential ↓
> > dopamine concentration↑
rTMS over the left primary motor cortex (M1)
Dopamine release in the ipsilateral putamen
Summary
Corticostriatal loops1.Prefrontal cortex The head of the caudate nucleus 2. Primary motor cortex Lateral putamen
Exp Brain Res 1998;120:114-28.
rTMS MDLFC M1
Dopamine ↑ Caudate Putamen
Discussion
Limited Interpretation of previous studies
• No detailed information about the coil position
• Inadequate control stimulation or comparison groups
• The blood-flow or metabolic measurements were acquired during a resting baseline
The goal of future studies
• Potential therapeutic effects of rTMS in depression, othe
r psychiatric and neurologic disorders
Improvement of the treatment protocols
Understand the pathophysiology of the brain disorders
Thanks for your attention ~~