Ramachandran Ramani MBBS, MD

Associate Professor of Anesthesiology; Director, Neuro Fellowship; Co-Director, Grand Rounds

Research Interests

Functional MRI under anesthesia; Mechanism of action of anesthetics; Central effects of anesthetic agents

Current Projects

1) Effect of 0.25 and 0.5 MAC sevoflurane on somatosensory and auditory activation - as studied with BOLD and rCBF measurement with fMRI.
2) Effect of low dose ketamine on frontal lobe function.
3) Case control study of periopertive blindness following spine surgery.

Research Summary

Understanding anesthesia through functional MRI

Functional MR imaging is an objective method of studying the subjective effects of anesthesia. It is a imaging tool being used widely by neuroscientist for studying functional activity in the CNS like speech, movement, visual / auditory activation etc. fMRI can measure BOLD (blood oxygen level dependent contrast) a qualitative measure of cerebral metabolism and regional cerebral blood flow (rCBF). BOLD and rCBF are indirect measures of neuronal activity.

In collaboration with the MRRC (magnetic resonance research center) we have been studying healthy ASA I volunteers under sevoflurane anesthesia. We study the effect of sevoflurane 0.25 and 0.5 MAC as well as the effect of activation under anesthesia. So far, close to 80 subjects have been imaged. In our first protocol the effect of visual, auditory and motor activation was studied under 0.25 MAC sevoflurane. Cerebral metabolism (BOLD) as well as rCBF was measured. Our conclusion from this study was - higher order association regions (like hippocampus, thalamus and cingulate gyrus) since they receive their input from multisynaptic pathways are much more sensitive to 0.25 MAC sevoflurane compared to unimodal association areas. Subsequently we studied the effect 0.25 and 0.5 MAC sevoflurane on auditory activation and memory activation. 0.25 MAC sevoflurane attenuates activation of auditory cortex while 0.5 MAC sevoflurane has profound effects on auditory cortex. This is of clinical relevance because auditory activation closely correlates with midlatency auditory evoked response which in turn correlates with amnesia under anesthesia. When specifically memory was activated both levels of sevoflurane anesthesia profoundly decreased the memory scores with loss of activation in the prefrontal cortex (primary site in the CNS for short term memory).

Extensive Research Description

Functional MR imaging is an objective method of studying the subjective effects of anesthesia. It is an imaging tool being used widely by neuroscientist for objectively studying functional activities in the CNS like speech, movement, visual / auditory activation, memory etc. With fMRI we can measure BOLD (blood oxygen level dependent contrast) a qualitative measure of cerebral metabolism and regional cerebral blood flow (rCBF). BOLD and rCBF are indirect measures of neuronal activity. Our aim in our fMRI anesthesia studies is to extend the utility of fMRI imaging tool for improving our understanding of the central effects of anesthesia. These studies have been in progress since 2003. In collaboration with the MRRC (magnetic resonance research center) we have been studying healthy ASA I volunteers under sevoflurane anesthesia. We have studied the central effects of sevoflurane anesthesia (0.5% and 1% sevoflurane equivalent to 0.25 MAC and 0.5 MAC) as well as the effect of functional activation under anesthesia. So far 60 subjects have been imaged.

1) In our first protocol the effect of visual, auditory and motor activation was studied under 0.25 MAC sevoflurane. Cerebral metabolism (BOLD) as well as rCBF was measured. Our conclusion from this study was – higher order association regions (like hippocampus, thalamus and cingulate gyrus) since they receive their input from multisynaptic pathways are much more sensitive to 0.25 MAC sevoflurane compared to the unimodal association areas.

2) Subsequently we studied the effect 0.25 and 0.5 MAC sevoflurane on auditory activation and memory activation. 0.25 MAC sevoflurane attenuated activation of the auditory cortex while 0.5 MAC sevoflurane exerted profound effects on the auditory cortex. This is of clinical relevance because auditory activation closely correlates with midlatency auditory evoked response which in turn correlates with amnesia under anesthesia.

3) When memory was activated (subjects heard a story presented over the headphones) both levels of sevoflurane anesthesia profoundly decreased the memory score in the subjects. fMRI imaging revealed decrease in activity in the thalamus and pre frontal cortex. However activation of the hippocampus persisted at 0.5 MAC sevoflurane. Clinically all the subjects were asleep and had no memory of any events at 0.5 MAC sevoflurane anesthesia.

4) The effect of 0.5 MAC sevoflurane on functional activity was studied with BOLD imaging. Low frequency oscillations in BOLD signals were compared in the awake and anesthesia state. Though subjects were asleep connectivity persisted in the thalamus at 0.5 MAC sevoflurane anesthesia.

We are presently studying the effect of somatosensory and auditory activation under 0.5 MAC sevoflurane anesthesia. We propose to study the effect of Propofol and Remifentanil in the future.


Selected Publications

  • Qiu M, Ramani R, Swetye M, Constable RT. Spatial non uniformity of the resting CBF and BOLD responses to sevoflurane – in vivo study of normal humans subjects with Magnetic Resonance Imaging. Hum Brain Mapp 2008; 29: 1390-1399
  • Qiu M, Ramani R, Swetye M, Rajeevan N, Constable RT. Anesthetic effects on regional CBF and BOLD and the coupling between task induced changes in CBF and BOLD – fMRI study in normal human subjects. Magn Reson Med 2008; 60: 987-996
  • Ramani R, Wardhan R. Understanding anesthesia through functional imaging. Curr Opin Anaesthesiol 2008: 21; 530-536
  • Ramani R. Vagus Nerve Stimulation therapy for seizures. J Neurosurg Anesthesiol 2008; 20: 29-35
  • Ramani R, Qiu M, Constable RT. Sevoflurane 0.25 MAC preferentially affects higher order association areas – fMRI study in volunteers. Anesth Analg 2007; 105: 648-655
  • Ramani R. Hypothermia for brain protection/resuscitation. Curr Opin Anaesthesiol 2006: 19; 487-491

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