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Nick L. Theodorou
Rutishauser et al. ‘Human memory strength is predicted by theta- frequency phaselocking of single neurons, Nature 464, 903 – 907 (2010)
a) The purpose of this investigation was to investigate the formation and
retrieval of memory by recording the activity of a population of single neurons. More
specifically this study chose to isolate brain oscillations in the theta frequency range
(3 – 8 Hz) as synaptic plasticity is induced, and analyse the synchronisation in terms
of phase between the local theta oscillation and the coordination of ‘spike’ timing.
Spikes of individual neurons timed against the local field potential (LFP) – the
‘coordinated action-potential timing across populations of neurons’. The LFP is the
favoured inducer of synaptic plasticity, and synaptic plasticity is thought to underlie
memory formation.
The group’s experimental techniques consisted of devising a memory test in order to
study the responses of nine human test subjects who had been previously evaluated
using standard neuropsychological tests. To record the single neuronal activity and the
local field potential (LFP), microwires were implanted into the hippocampus and
amygdale, part of a technique known as Electrophysiology. The theoretical techniques
employed were primarily data analysis for: behaviour; spike sorting; estimation of
phase-locking; phase-reset analysis; and spike-field coherence (SFC).
The results showed that most neurons are phase locked to the LFP at a frequency
within the theta range of 3Hz – 8Hz when subjects recalled the stimuli in the test.
Thus the group considered whether a neuron spike phase locked with the LFP during
learning could predict whether the subject will store a memory of the image and recall
it successfully, which was shown to be the case, with good confidence.
Nick L. Theodorou
Rutishauser et al. ‘Human memory strength is predicted by theta- frequency phaselocking of single neurons, Nature 464, 903 – 907 (2010)
b) The experiment was developed to test the existence of a relationship between
LFP/spike timing and successful memory recall. The underlying aim was to learn
more about memory formation by putting forward a reasonable hypothesis: During
memory retrieval a substantial fraction of neurons produce spikes which are phaselocked with the theta range (3 – 8 Hz) of the Local Field Potential (LFP), can an
increase of phase-locked spikes during learning predict an increase in memory
retrieval strength? The investigation is important because a fuller understanding of
memory formation would have many medical applications, especially in developing
treatments for brain trauma or epilepsy.
The group developed a memory test of two parts, learning and recognition. Patients
were given a set of 100 previously unseen images, and then patients viewed a set of
100 where 50 were previously unseen and 50 were part of the previous set. During the
viewing of the second set, patients decided on a six point confidence scale whether
they had seen the image before or not. 1 = new, confident; 2 = new, probably; 3 =
new, guess; 4 = old, guess; 5 = old, probably; 6 = old, confident. To observe brain
oscillations, microwires were implanted into the amygdala and hippocampus - the two
brain regions where the single-unit neuronal activity and the low frequency
oscillations in the LFP would be monitored; a method called electrophysiology.
To segregate the data from the recognition part of the test, the 50 images previously
seen were characterised into remembered or forgotten; true positive or false negative.
Then the neuronal activity was compared between true positive or false negative.
The spike field coherence (SFC), which varies as a function of frequency and is
presented as a value between 0% and 100%, was computed to examine the timing
relationship the group suggested. If the SFC is larger, the more accurate it can be said
that a spike follows a particular phase. When the group found a difference between
Nick L. Theodorou
Rutishauser et al. ‘Human memory strength is predicted by theta- frequency phaselocking of single neurons, Nature 464, 903 – 907 (2010)
the two trials of true positive (TP) or false negative (FN), as a control, the label of TP
or FN was randomly reassigned and the analysis re-conducted. A notable result was
found, the theta range SFC for TP was ~50% higher than that for FN. Further data
analysis was conducted using the spike-triggered average (STA) which is constructed
by averaging LFP segments of ± 400 ms centred on every spike. If a logical
relationship between the spike timing and LFP exists, the resulting trace will deviate
from zero. Strong oscillations in the theta range were seen in each of the significantly
phase locked neurons. For intelligible results to be computed the STA was equalised
for number of spikes; this was how differences in phase locking were computed. The
group found that the power of LFP when the spike occurred did not distinguish
between TP and FN.
There is no consensual theory for the group to compare their experimental results
with; however the results indicate further evidence for the association of the theta
range with synaptic plasticity as it was boasted as the most prevalent frequency range.
The experiment warrants a large discussion of what data is conclusive.
The group considered their subjects to have a good sense of the quality of their
memories as confidence mapped well on to performance and data analysis arguments
were rechecked against the formulated control of random label assignment. However,
the experiment did not wholly consider the aspect of behavioural memory; the novelty
of the pictures, and the attention and arousal of the patients. The uncertainties that
accompany the argument of ‘phase locked’ are large, but not discussed. Therefore the
major insight gained is that sometimes in an experiment it can be difficult to grasp the
full physical interpretation, and sometimes relationships can be forged from statistics,
but a clear trend such as the asymmetry between the TP and FN results can be found
from the raw data, and thus are ‘true’ until a more accurate experiment can falsify it.