You’ll feel better in the morning: Sleep deprivation disconnects the emotional brain January 27, 2008Posted by Johan in Emotion, Neuroscience, Sleep.
Disturbed sleep patterns feature in a range of psychiatric disorders, many of which fall under the DSM’s mood disorder category. A recent paper by Yoo et al (2007) suggests that sleep deprivation itself can produce abnormal affective processing. In other words, sleep disturbances may be a cause as well as a symptom in conditions such as depression.
Yoo et al (2007) approached this issue with fMRI. Brain scans were taken of one participant group who had been sleep deprived for 35 hours, and one group who had slept normally. The participants viewed emotional pictures from a standardised set (the international affective picture system), which varied gradually in valence from neutral to aversive.
Yoo et al approached the imaging analysis with a few theoretical notions, which formed the basis of the brain areas that they investigated more closely. First, the amygdala is believed to mediate the emotional response to the aversive pictures, and secondly, it is argued that responding in the amygdala is mediated by an inhibitory projection from medial prefrontal cortex (a frequently invoked projection – see this related post).
To address the first issue, Yoo et al compared the amygdala response to the aversive pictures in the two groups. The amygdala was more activated bilaterally in the sleep-deprived group, and furthermore, a larger volume of amygdala was activated in this group as the figure at the top of this post shows. Note that the neutral pictures elicited no greater amygdala responses in the sleep-deprived group, so this is a case of greater amygdala re-activity, rather than an increase in baseline responding.
The role of medial prefrontal cortex in mediating the amygdala reactivity was investigated by measuring the regions that showed functional connectivity with the amygdala during the task. The method isn’t straightforward, but essentially it’s based on taking the activity in the amygdala voxels, and assessing which other brain regions show responses that covary. The results are given as a contrast between the two groups.
As the yellow bits in the figure show, the sleep control group displayed stronger amygdala-prefrontal connectivity than the sleep-deprived group. Conversely, the amygdala had stronger connectivity with various regions of the brainstem in the sleep deprived group compared to the sleep control group.
So to re-cap: sleep-deprived participants showed larger amygdala responses, and their amygdalas showed weaker functional connectivity with medial prefrontal cortex. This finding does not prove that the greater amygdala response in the sleep-deprived group was caused by the weakened connectivity with medial prefrontal cortex, but it is certainly consistent with that notion. Yoo et al suggest that sleep acts as a kind of reset of brain reactivity, to ensure that emotional challenges can be met appropriately. But why is such a reset necessary in the first place? Why is the regulatory influence of medial prefrontal cortex weakened by sleep deprivation? The role of sleep in affect is only beginning to be understood.
Yoo, S-S., Gujar, N., Hu, P., Jolesz, F.A., & Walker, M.P. (2007). The human emotional brain without sleep – a prefrontal amygdala disconnect. Current Biology, 17, 877-878.
Using TMS to evoke slow waves during sleep May 16, 2007Posted by Johan in Neuroscience, Sleep.
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During non-REM sleep, in stages 2-4, the neurons in the cortex fire in near synchrony, at a rate of about one per second. This is known as slow wave sleep, and is thought to be important for various processes, including memory consolidation (see a previous related post).
Simply put, TMS is produced by a very strong electromagnet, capable of sending out controllable pulses. If held close to the head, the pulses depolarize neurons on the surface of the cortex, thus producing a single burst of activation. TMS is most often used to disrupt processing by applying a repetitive pulse, which incapacitates that part of the cortex temporarily. This is a very powerful technique, as it allows the researcher to infer that the brain region has a causal role in the behaviour that is being measured, unlike fMRI and other neuroimaging measures where only a correlation between brain activation and behaviour can be made. However, in this study, TMS was used for a somewhat different purpose.
While the participants were in non-REM sleep, TMS was applied. EEG recordings showed the effect of this on the brain. Each TMS pulse tiggered a single slow wave, which left in its wake a drop in activity to levels similar to what is observed while recovering from sleep deprivation (this according to the authors). In terms of the stages of sleep, the activity while TMS was on was classified by independent raters as stage 4, while the recording when it was off was rated as stage 2.
It’s worth emphasising that the participants were already in non-REM sleep, where slow waves normally occur. The crucial finding in this study is that TMS made it possible to control when these slow waves occur. The same stimulation did not evoke slow waves when the participants were awake.
Unlike the normal slow waves, which can originate from various parts of the cortex, the TMS-induced slow waves all originated from the site of the coil (perhaps unsurprisingly), which was placed over sensorimotor cortex, with the coil almost straight on top of the head (see the red cross in the figure below). The investigators found no other location that could induce slow waves as reliably. However, many parts of the head could not be tested as stimulating them produced muscle movements, so this does not necessarily mean that sensorimotor cortex is crucial in producing spontaneous slow waves. The figure below shows the positioning of the coil, and the EEG activation patterns during evoked and spontaneous slow waves.
Note that while the high rate of stimulation makes the TMS slow waves seem quite unlike the spontaneous slow waves, the individual slow waves that TMS produced (compare the graphs in the red boxes to the graph in the blue box) are quite similar to those of spontaneous slow waves. The figure at the top, showing the average slow waves produced spontaneously or by stimulation, makes this point quite clear.
For anyone who knows how loud TMS can be, you might wonder how the participants managed to sleep through this study. The researchers went through some trouble to ensure that the click that the TMS produces when it discharges was imperceptible: they created an opposing waveform of the click noise that was played to the participants through headphones, thus masking the sound. A foam layer was also used to prevent bone conduction of the sound. Despite these precautions, I’m more than a little impressed by the ability of these participants to sleep soundly, knowing some guys in white coats are about to start sending pulses through your head as soon as you pass out.
More than anything else, this paper is a description of a new method. I’m not sure that we’ve learned a lot about how slow waves are produced or what purpose they serve, but with the method outlined by Massimini et al (2007), future investigators may be able to expand on this. This application of TMS allows you to vary the rate of the slow waves, and measure how this affects the various functions that slow wave sleep is believed to involve. Much like the repetitive-TMS application I outlined above, this means that causal relationships can be inferred.
Massimini, M., Ferrarelli, F., Esser, S.K., Riedner, B.A., Huber, R., Murphy, M., Peterson, M.J., & Tononi, G. (2007). Triggering sleep slow waves by transcranial magnetic stimulation. PNAS, 104, 8496-8501.
How does the Hippocampus interface with Cortex? March 9, 2007Posted by Johan in Neuroscience, Connectionism, Neural Networks, Sleep.
Hahn, Sakmann & Meta report some intriguing results, for now only available in a press release, as PNAS apparently offers no ahead of print feature. A related paper by the same group (Hahn, Sakmann & Mehta, 2006) is available, however, which is where I got the micrograph of a cell in hippocampal area CA1 that you see above.
Hahn et al anesthetised rats to simulate deep sleep, while recording the activity of cells in the hippocampus and cortex simultaneously. They found that excitatory activity in the cortex produced an echo in hippocampal cells. The pattern of activity in the hippocampus was not uniform: cells in the dentate gyrus showed a strong response, CA3 region cells showed a weaker response, and CA1 region cells were seemingly inhibited by the cortical activity.
One reason why this is interesting is that a popular theory of memory consolidation makes the opposite prediction, that is, the hippocampus should largely drive cortical activation. In the connectionist model of McClelland, McNaughton and O’Reilly (1995), the hippocampus is positioned as the “trainer” of long-term memory structures in the cortex.
The “trainer” role for the hippocampus arose from the observation that while a single connectionist network can easily accommodate large amounts of information, incrementally adding new items causes catastrophic interference. Simply put, this occurs because when new memories are formed by changing the connection weights in the network, the older memory traces are disrupted, since they relied on the previous weightings. By positing a second network that uses more easily changeable connection weights to allow for rapid learning, interleaved learning is made possible.
In this view, then, the hippocampus acquires new information rapidly, after which it trains the larger and slower cortical network on the new information. The hippocampus interleaves this new information with re-activation of older memories, which allows the old and new memories to co-exist in the cortical network, without catastrophic interference. McClelland et al suggested that this consolidation process occurs during slow-wave sleep.
To tie this in with Hahn et al’s results, the cortex-driven hippocampal activation could be viewed speculatively as the re-activation of memory traces described in the McClelland et al model. But it’s hard to see how the hippocampus then “trains” the cortical network on new informaton, when no activity seems to go in this direction. This leaves us with the possibility that this hippocampus-driven training of the cortical network occurs at a different point in the circadian cycle, or with the more bleak possibility that there is something fundamentally wrong with the functional division that McClelland et al proposed.
In any case, the method used by Hahn et al is quite fascinating. Up until now, very little has been known about how the hippocampus interacts with the cortex to play its (disputed!) role in memory formation and consolidation. The paper in PNAS is definitely one to look out for.
The Mehta Lab’s publications at Brown
Hahn, T.G., Sakmann, B., & Mehta, M.R. (2006). Phase-locking of hippocampal interneurons’ membrane potential to neocortical up-down states. Nature Neuroscience, 9, 1359-1361.
McClelland, J.L., McNaughton, B.L., & O’Reilly, R.C. (1995). Why There are Complementary Learning Systems in the Hippocampus and Neocortex: Insights from the Successes and Failures of Connectionist Models of Learning and Memory. Psychological Review, 102, 419-457.
Sleep Deprivation and the Hippocampus February 10, 2007Posted by Johan in Neuroscience, Sleep.
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It is quite striking that we currently have no strong account of the purpose of an activity that we all spend somewhere between a quarter and a third of our lives engaging in: sleep. However, it’s not fair to say that we don’t know why we sleep: sleep has been found to affect a range of behaviours. These various purposes that sleep serves may be exactly the reason why a singular account that explains sleep has not been forthcoming. It’s possible that sleep is necessary for several more-or-less independent processes.
Some “creative” functions of sleep such as physical restoration (implausible, as measurable effects of deprivation only appear after extremely prolonged sleep deprivation) and adaptation (in this view, animals are better off sleeping away down-time when they don’t need to feed, as this keeps them out of harm’s way) have been proposed, but the main functions that appear to have tangible effects in experiments concern development and memory.
According to developmental accounts, REM sleep deprivation in developing organisms results in behavioral problems, decreased brain mass, and neuronal cell death. Researchers that focus on the role of sleep in memory suggest that sleep is essential for consolidating information in long-term memory, possibly with relation to emotional content: A recent paper reported on an experiment where participants read texts with emotional or neutral content, followed by three hours of sleep or waking. When testing recognition four years later (!), the participants who had slept immediately after encoding showed a recognition advantage for the emotional stories, but not for the neutral ones (Wagner et al, 2006). Participants who had been awake following encoding showed no such recognition advantage.
Results obtained by Mirescu et al (2006) exemplifies the possibility that developmental and memory accounts are related. In this study, rats were deprived of sleep while their levels of the hormone corticosterone were either held constant or unmanipulated. Mirescu et al (2006) reported that rats who are deprived of sleep in this manner showed reduced cell proliferation in the hippocampus (which appears to be a critical area for encoding events into long-term memory), but this effect was mediated by corticosterone: rats who had their corticosterone levels held constant did not show inhibited cell proliferation. This suggests that sleep deprivation affects normal functioning of the hippocampus, and that corticosterone may be the causative factor… Although this only pushes the question back to what causes corticosterone levels to increase during sleep deprivation. It would be quite interesting to replicate this study in a developmental framework, with memory tests. Sleep deprived rats with constant corticosterone levels may not show the memory impairments that normally appear in rats who have been subjected to extended sleep deprivation.
By the way, it’s worth emphasising that these rats had had no sleep for 72 hours: no effects appeared for rats that had been deprived of sleep for 24 hours. So if you’re wondering if these results suggest that you should start getting more sleep, the answer is probably going to be no, at least not for this reason.
Mirescu, C., Peters, J.D., Noiman, L., & Gould, E. (2006). Sleep Deprivation Inhibits Adult Neurogenesis in the Hippocampus by Elevating Glucocorticoids. Proceedings of the National Academy of Sciences of the United States of America, 103, 19170-19175.
Wagner, U., Hallschmid, M., Rasch, B., & Born, J. (2006). Brief Sleep after Learning Keeps Emotional Memories Alive for Years. Biological Psychiatry, 60, 788-790