Buchel, C., Morris, J., Dolan, R.J., & Friston, K.J. (May 1998). Brain systems mediating aversive conditioning: an event-related fMRI study. Neuron, Vol. 20, 947-957.
Classical conditioning refers to a type of associative learning whereby a previously neutral stimulus (CS) comes to elicit a behavioral response by being paired with an aversive unconditioned stimulus (US). This study implemented a human classical conditioning paradigm in which images of faces (CS) were paired with an aversive tone (US). To assess which areas of the brain were related to conditioning, event-related fMRI responses were compared between presentation of conditioned stimuli (CS+) and unconditioned stimuli (CS-) after skin conductance indicated the conditioning regimen was completed successfully. To be more accurate, CS- was compared to the occasional trials of CS+ which were not followed by a tone.
Unequivocal differential responses were found in two cortical areas: the anterior cingulate cortex (ACC) and the anterior insula. These structures receive input from the amygdala, which also shows interesting activation patterns during this paradigm. The lateral amygdala in particular shows time-dependent neural responses, with higher than baseline responses at first but habituating over time. A possible explanation is a negative feedback loop, an analgesia kicked off by the amygdala and mediated by endogenous opioids which leads to reduced conditioning over time. Finally, differential activation was also witnessed in the red nucleus together with premotor structures, characteristic of response expression.
Happy 50th post!!! And happy bissextile day!!!
Friday, February 29, 2008
Wednesday, February 27, 2008
Conflict Monitoring and the ACC
Botvinick, M.M., Cohen, J.D., & Carter, C.S. (December 2004). Conflict monitoring and anterior cingulate cortex: An update. Trends in Cognitive Sciences, Vol. 8, No. 12, 539-546.
Activity in the dorsal anterior cingulate cortex (ACC) shows up in a variety of tasks. For example, a transient potential (known as the error-related negativity, or ERN) is elicited from the posterior ACC in response to error commission. And a similar evoked potential, the feedback-related negativity (FRN), occurs in response to error feedback and may derive from the same portion of the cingulate that generates the ERN. These activity patterns during commission of errors led researchers to suggest an 'error detection' function for the ACC.
However, tasks which require overriding of habitual responses and tasks which require selecting among a set of equally permissible responses also yield ACC activation. This led researchers to put forth a 'conflict detection' theory of ACC function, with the structure being especially responsible for selecting between competing motor responses.
However, recent studies have proposed other unifying theories to explain the role of the ACC beyond just error detection and conflict monitoring. Some suggest the ACC serves to evaluate action outcomes, performing cost-benefit analyses on possible outcomes and using reward-related information to guide action selection. This 'action-outcome evaluation' view is particularly consonant with other research connecting the mesencephalic dopamine system with the ACC in reinforcement learning.
Activity in the dorsal anterior cingulate cortex (ACC) shows up in a variety of tasks. For example, a transient potential (known as the error-related negativity, or ERN) is elicited from the posterior ACC in response to error commission. And a similar evoked potential, the feedback-related negativity (FRN), occurs in response to error feedback and may derive from the same portion of the cingulate that generates the ERN. These activity patterns during commission of errors led researchers to suggest an 'error detection' function for the ACC.
However, tasks which require overriding of habitual responses and tasks which require selecting among a set of equally permissible responses also yield ACC activation. This led researchers to put forth a 'conflict detection' theory of ACC function, with the structure being especially responsible for selecting between competing motor responses.
However, recent studies have proposed other unifying theories to explain the role of the ACC beyond just error detection and conflict monitoring. Some suggest the ACC serves to evaluate action outcomes, performing cost-benefit analyses on possible outcomes and using reward-related information to guide action selection. This 'action-outcome evaluation' view is particularly consonant with other research connecting the mesencephalic dopamine system with the ACC in reinforcement learning.
Pain and emotion interactions in subregions of the cingulate gyrus
Vogt, B.A. (July 2005). Pain and emotion interactions in subregions of the cingulate gyrus. Nature Neuroscience Reviews, Volume 6, 533-544.
Beyond Brodmann's simplistic account of the cingulate gyrus with two divisions, recent cytoarchitectural studies favor a four-region model based on connections and function. This includes the ACC, the MCC, the PCC, and the RSC. This new theoretical construct, in conjunction with new neuroimaging data, is shedding light on the cingulate's role in pain and emotion processing.
Regarding emotion, it seems that the cingulate cortex processes emotion differentially.
Beyond Brodmann's simplistic account of the cingulate gyrus with two divisions, recent cytoarchitectural studies favor a four-region model based on connections and function. This includes the ACC, the MCC, the PCC, and the RSC. This new theoretical construct, in conjunction with new neuroimaging data, is shedding light on the cingulate's role in pain and emotion processing.
Regarding emotion, it seems that the cingulate cortex processes emotion differentially.
- ACC - Activity during sadness is greatest in the sACC, believed to be important for storage of negatively valenced memories, and which has projections to subcortical autonomic centers. Happiness tends to elicit activity in the pACC, but this is not an autonomic integration center.
- MCC - Fear is associated with activity in the aMCC, the only cingulate structure to receive input from amygdala.
- PCC - The vPCC also shows activity during happiness, but is believed to be characterized by the assessing the self-relevance of emotional events (an emotional pre-processor).
- RSC - The RSC is still poorly understood but is believed to play a role in memory access of valenced information.
- MCC - It appears the aMCC could be related to fear-avoidance behaviors (as alluded to above). More posteriorly, activations in the pMCC evoke skeletomotor body orientations but without affective (autonomic) or emotional (valenced) content.
- PCC - The dPCC, likewise, seems to be involved in orienting the body in response to noxious sensory stimuli.
Tuesday, February 26, 2008
Deep brain stimulation for treatment-resistant depression
Mayberg et al. (March 3, 2005). Deep brain stimulation for treatment-resistant depression. Neuron, Vol. 45, 651-660.
This experiment exposed a small sample of six people with treatment-resistant depression to deep brain stimulation (DBS) in the subgenual cingulate region (BA25), known to be a critical region for modulating negative mood states, and showing elevated activity in these refractory patients.
Acute effects of stimulation included sudden mood change (reduced negative and increased positive scores), as well as improvements in interest and activity level. Upon continued use, sleep patterns were among the first of the normalized symptoms, followed by increased energy, interest and pleasure in social activity, decreased apathy and anhedonia, and improved planning abilities. Upon discontinuation of chronic treatment, mood improvements tended to persist, whereas cognitive aspects of depression (e.g. poor concentration, apathy) did not, perhaps indicating differential effects on different connected systems.
These results, showing a sustained remission of depression in four out of six patients who previously failed to respond to medications, psychotherapy, and ECT, still warrant further investigation (for starters, a larger sample size) but do favor a positive interpretation of the efficacy of DBS for people with refractory depression. With its connections to brainstem, hypothalamus, and insula (read: sleep, appetite, libido, and neuroendocrine effects) and reciprocal pathways to the orbitofrontal/medial prefrontal cortices and the anterior and posterior cingulate cortices (read: influences on learning, memory, reward, and motivation), this study also sheds light on the subgenual cingulate region as a critical node of a distributed mood-regulatory network involved in major depression.
This experiment exposed a small sample of six people with treatment-resistant depression to deep brain stimulation (DBS) in the subgenual cingulate region (BA25), known to be a critical region for modulating negative mood states, and showing elevated activity in these refractory patients.
Acute effects of stimulation included sudden mood change (reduced negative and increased positive scores), as well as improvements in interest and activity level. Upon continued use, sleep patterns were among the first of the normalized symptoms, followed by increased energy, interest and pleasure in social activity, decreased apathy and anhedonia, and improved planning abilities. Upon discontinuation of chronic treatment, mood improvements tended to persist, whereas cognitive aspects of depression (e.g. poor concentration, apathy) did not, perhaps indicating differential effects on different connected systems.
These results, showing a sustained remission of depression in four out of six patients who previously failed to respond to medications, psychotherapy, and ECT, still warrant further investigation (for starters, a larger sample size) but do favor a positive interpretation of the efficacy of DBS for people with refractory depression. With its connections to brainstem, hypothalamus, and insula (read: sleep, appetite, libido, and neuroendocrine effects) and reciprocal pathways to the orbitofrontal/medial prefrontal cortices and the anterior and posterior cingulate cortices (read: influences on learning, memory, reward, and motivation), this study also sheds light on the subgenual cingulate region as a critical node of a distributed mood-regulatory network involved in major depression.
dlPFC promotes LTM formation via WM organization
Blumenfeld, R.S. & Ranganath, C. (January 18, 2006). Dorsolateral prefrontal cortex promotes long-term memory formation through its role in working memory organization. The Journal of Neuroscience, 26, 3, 916-925.
This paper speculates that the different regions of the prefrontal cortex contribute differentially to working memory (WM). Specifically, they argue that the dorsolateral prefrontal cortex (dlPFC) is recruited during tasks requiring organization of items active in WM, while the ventrolateral prefrontal areas (vlPFC) are involved in WM maintenance, or simply holding items in short-term memory.
The study begins behaviorally by showing that overall memory is increased during tasks which require organization by re-ordering (in comparison to tasks which are merely rehearsals). Single items encoded on re-ordering trials were significantly more likely to be judged as "remembered" than from rehearsal trials. And organization of items during re-ordering trials resulted in much higher recollection together, suggesting the strengthening of associative links between items in these organization trials. Then the paper shifts to the fMRI data to attempt to implicate the dlPFC specifically. Their evidence: the dlPFC showed increased activation during the delay (encoding) period of re-ordering trials relative to rehearse trials.
However, one very possible alternative explanation is the effect of nonspecific factors correlated with task difficulty. Reorder and rehearse trials differ in a number of ways, difficulty being the most significant. Perhaps the increased attention required in the re-ordering trials led to changes in behavioral results and a general increase in activation in the dlPFC (and elsewhere). This raises concerns that the activity in the dlPFC could be attributed to processes other than organization.
This paper speculates that the different regions of the prefrontal cortex contribute differentially to working memory (WM). Specifically, they argue that the dorsolateral prefrontal cortex (dlPFC) is recruited during tasks requiring organization of items active in WM, while the ventrolateral prefrontal areas (vlPFC) are involved in WM maintenance, or simply holding items in short-term memory.
The study begins behaviorally by showing that overall memory is increased during tasks which require organization by re-ordering (in comparison to tasks which are merely rehearsals). Single items encoded on re-ordering trials were significantly more likely to be judged as "remembered" than from rehearsal trials. And organization of items during re-ordering trials resulted in much higher recollection together, suggesting the strengthening of associative links between items in these organization trials. Then the paper shifts to the fMRI data to attempt to implicate the dlPFC specifically. Their evidence: the dlPFC showed increased activation during the delay (encoding) period of re-ordering trials relative to rehearse trials.
However, one very possible alternative explanation is the effect of nonspecific factors correlated with task difficulty. Reorder and rehearse trials differ in a number of ways, difficulty being the most significant. Perhaps the increased attention required in the re-ordering trials led to changes in behavioral results and a general increase in activation in the dlPFC (and elsewhere). This raises concerns that the activity in the dlPFC could be attributed to processes other than organization.
Changes in Hippocampi of Taxi Drivers
Maguire et al. (April 11, 2000). Navigation-related structural change in the hippocampi of taxi drivers. PNAS, Vol. 97, No. 8, 4398-4403.
This correlational study showed taxi drivers had a significantly greater volume in the posterior hippocampus, whereas control subjects showed greater volume in the anterior hippocampus. Authors interpret the results as evidence for the relative redistribution of gray matter in the hippocampus in response to the occupational need to store increasingly detailed spatial representations. The amount of time spent as a taxi driver was found to be correlated with the amount of volume in the right posterior hippocampus, suggesting that while mental spatial maps are likely to be stored in the posterior hippocampus and necessitate progressive structural changes over time, the left hippocampus may participate in spatial navigation and memory differently from the right.
This correlational study showed taxi drivers had a significantly greater volume in the posterior hippocampus, whereas control subjects showed greater volume in the anterior hippocampus. Authors interpret the results as evidence for the relative redistribution of gray matter in the hippocampus in response to the occupational need to store increasingly detailed spatial representations. The amount of time spent as a taxi driver was found to be correlated with the amount of volume in the right posterior hippocampus, suggesting that while mental spatial maps are likely to be stored in the posterior hippocampus and necessitate progressive structural changes over time, the left hippocampus may participate in spatial navigation and memory differently from the right.
Wednesday, February 20, 2008
Neural fate of ignored stimuli
Yi, D. et al. (September 2004). Neural fate of ignored stimuli: dissociable effects of perceptual and working memory load. Nature Neuroscience, Volume 7, Number 9, 992-996.
After some debate over whether attention acts a filter early in the processing hierarchy ("early selection") or whether it blocks awareness of perceptually encoded stimuli at a late stage of processing ("late selection"), the field has accepted both accounts to some degree. When task difficulty is low, late selection may be more likely, whereas aggressive early selection may be more common when task difficulty is high. However, task difficulty can be defined in several ways and this paper predicted and confirmed that increasing perceptual demands properly constitutes task difficulty and leads to this early selection behavior, whereas increasing working memory loads does not.
Experimentally, subjects were shown faces foveally, surrounded by background images depicting scenes. They were told to fixate on the faces and ignore the background images. Faces were cycled, but so were the background images. In the EASY block, subjects were asked to play a "one-back" game, discriminating between the current face image and face presented prior. Subject performance was high. However, in addition to this primary task, the parahippocampal place area (PPA) showed activity that indicated it was indeed processing the background image changes successfully as well. But as the perceptual load was adjusted, with the HARD block requiring more difficult facial discriminations, it was clear that the PPA was not processing the background scenes to the same extent as in the low perceptual load condition. By comparison, the MEMORY block, in which "two-back" rules required subjects to maintain more information in working memory for longer, did not demonstrate these attenuation effects on background processing, i.e. the PPA was still successfully detecting background changes. This indicated, as hypothesized, that perceptual demands and working memory load result in differential attentional effects.
After some debate over whether attention acts a filter early in the processing hierarchy ("early selection") or whether it blocks awareness of perceptually encoded stimuli at a late stage of processing ("late selection"), the field has accepted both accounts to some degree. When task difficulty is low, late selection may be more likely, whereas aggressive early selection may be more common when task difficulty is high. However, task difficulty can be defined in several ways and this paper predicted and confirmed that increasing perceptual demands properly constitutes task difficulty and leads to this early selection behavior, whereas increasing working memory loads does not.
Experimentally, subjects were shown faces foveally, surrounded by background images depicting scenes. They were told to fixate on the faces and ignore the background images. Faces were cycled, but so were the background images. In the EASY block, subjects were asked to play a "one-back" game, discriminating between the current face image and face presented prior. Subject performance was high. However, in addition to this primary task, the parahippocampal place area (PPA) showed activity that indicated it was indeed processing the background image changes successfully as well. But as the perceptual load was adjusted, with the HARD block requiring more difficult facial discriminations, it was clear that the PPA was not processing the background scenes to the same extent as in the low perceptual load condition. By comparison, the MEMORY block, in which "two-back" rules required subjects to maintain more information in working memory for longer, did not demonstrate these attenuation effects on background processing, i.e. the PPA was still successfully detecting background changes. This indicated, as hypothesized, that perceptual demands and working memory load result in differential attentional effects.
Tuesday, February 19, 2008
Molecular Mechanisms of Memory Storage
Hawkins, R.D., Kandel, E.R., & Bailey, C.H. (June 2006). Molecular Mechanisms of Memory Storage in Aplysia. Biological Bulletin, 210, 174-191.
This article reviews what molecular biology currently knows about the underlying nervous system mechanisms for memory. Memory comes in several forms. The short-term form, kicked off by brief and well-spaced stimulation pulses, lasts minutes and involves alterations in the effectiveness of existing synaptic connections. This can be accomplished via covalent modifications of pre-existing proteins by a variety of kinases, enhanced neurotransmitter release, and other means of short-term sensitization which increase the excitability of the neuron pair. The intermediate form, created by repeated and more prolonged exposure to stimulation, lasts hours and often requires translation-but-not-transcription-dependent processes. The final and most stable phase of long-term memory storage is characterized by the modulation of both function and structure of specific synaptic connections. This form, lasting days, weeks, or longer, requires full gene expression for synaptic remodeling and the growth of new synaptic connections. The mechanisms, though varied, together create a continuum between short- and long-term memory storage. (Other changes, such as increases in spine size, increases in the size and number of synaptic vesicles, or the clustering of such vesicles, can be seen along this spectrum.)
The paper also mentions the significance of synaptic tagging mechanisms discovered only recently. Given that many of these methods of potentiation kick off cell-wide processes, being able to identify the specific synapse whose activation originally triggered these processes is extremely important. (More here)
Finally, the article talks about potential memory longevity concerns. Since biological molecules have a short half-life (hours to days) compared to the duration of memory (up to years), researchers hoped to better understand the self-sustaining properties of memory. CPEB, which is a prion-like protein and is known to take two different conformational states, has an active state which has the ability to "awaken" dormant mRNAs to initiate translation at the local activated synapse. CPEB, in addition to being proposed as a synaptic marker, also seems to be a good candidate for sustained synapse-specific potentiation since it is also known to self-perpetuate once active. CPEB-3 has been found in mammal hippocampus and is induced by dopamine.
This article reviews what molecular biology currently knows about the underlying nervous system mechanisms for memory. Memory comes in several forms. The short-term form, kicked off by brief and well-spaced stimulation pulses, lasts minutes and involves alterations in the effectiveness of existing synaptic connections. This can be accomplished via covalent modifications of pre-existing proteins by a variety of kinases, enhanced neurotransmitter release, and other means of short-term sensitization which increase the excitability of the neuron pair. The intermediate form, created by repeated and more prolonged exposure to stimulation, lasts hours and often requires translation-but-not-transcription-dependent processes. The final and most stable phase of long-term memory storage is characterized by the modulation of both function and structure of specific synaptic connections. This form, lasting days, weeks, or longer, requires full gene expression for synaptic remodeling and the growth of new synaptic connections. The mechanisms, though varied, together create a continuum between short- and long-term memory storage. (Other changes, such as increases in spine size, increases in the size and number of synaptic vesicles, or the clustering of such vesicles, can be seen along this spectrum.)
The paper also mentions the significance of synaptic tagging mechanisms discovered only recently. Given that many of these methods of potentiation kick off cell-wide processes, being able to identify the specific synapse whose activation originally triggered these processes is extremely important. (More here)
Finally, the article talks about potential memory longevity concerns. Since biological molecules have a short half-life (hours to days) compared to the duration of memory (up to years), researchers hoped to better understand the self-sustaining properties of memory. CPEB, which is a prion-like protein and is known to take two different conformational states, has an active state which has the ability to "awaken" dormant mRNAs to initiate translation at the local activated synapse. CPEB, in addition to being proposed as a synaptic marker, also seems to be a good candidate for sustained synapse-specific potentiation since it is also known to self-perpetuate once active. CPEB-3 has been found in mammal hippocampus and is induced by dopamine.
Sunday, February 17, 2008
Control of goal-directed and stimulus-driven attention
Corbetta, M. & Shulam, G.L. (March 2002). Control of goal-directed and stimulus-driven attention in the brain. Nature Reviews Neuroscience, Volume 3, 201 - 215.
This paper proposes that visual attention (orienting) is controlled by two interacting networks. One system which is centered on the dorsal posterior parietal and frontal cortex, is involved in the cognitive, top-down, goal-directed selection of sensory information and responses. The second system, largely lateralized to the right hemisphere, is centered on the temporoparietal and ventral frontal cortex and is specialized for the detection of behaviorally-relevant stimuli, particularly when they are salient or unexpected. The second network reflects stimulus-driven, bottom-up control of attention, and can be seen as a 'circuit-breaker' of the first network, interrupting ongoing cognitive activity and directing attention to stimuli outside the focus of current processing when necessary.
This paper proposes that visual attention (orienting) is controlled by two interacting networks. One system which is centered on the dorsal posterior parietal and frontal cortex, is involved in the cognitive, top-down, goal-directed selection of sensory information and responses. The second system, largely lateralized to the right hemisphere, is centered on the temporoparietal and ventral frontal cortex and is specialized for the detection of behaviorally-relevant stimuli, particularly when they are salient or unexpected. The second network reflects stimulus-driven, bottom-up control of attention, and can be seen as a 'circuit-breaker' of the first network, interrupting ongoing cognitive activity and directing attention to stimuli outside the focus of current processing when necessary.
Saturday, February 16, 2008
Direct and indirect activation effects on reconsolidation in amygdala
Debiec, J., Doyere, V., Nader, K., LeDoux, J.E. (February 28, 2006). Directly reactivated, but not indirectly reactivated, memories undergo reconsolidation in the amygdala. PNAS, Volume 103, Number 9, 3428-3433.
The first experiment of the paper used second-order fear conditioning (SOFC) to create an associative memory network in rat brain. To do this, a conditioned stimulus (CS1) is paired with an unconditioned stimulus (US), which naturally elicits a response. After pairing, now CS1 elicits the response (such as freezing in fear). This is the first-order conditioning. Now, a second conditioned stimulus (CS2) is paired with CS1, and by association elicits the response transitively. When extinction of CS1 responding does not affect the responding of CS2, CS2 is considered independent of the first-order fear memory. But if CS2 responding decreases with CS1 extinction, then we have an associative chain (CS2 --> CS1 --> US).
The second experiment, building on such a conditioning chain, discovered that extinction of freezing responses to the first-order stimulus (CS1) leads to responding impairments in CS2. Extinction of the second-order stimulus (CS2), does not have any effect on CS1. This builds a case for a hierarchical, uni-directional chain.
The last experiment examined the effect of activation (memory retrieval) on such an associative chain. (In another paper, Nader and LeDoux showed that reactivation of a memory places it in a labile state -- that is, susceptible to disruption -- until again reconsolidated.) Results demonstrated that protein synthesis inhibition after exposure to a single CS1 impairs responses to both CS1 and CS2. But protein synthesis inhibition after exposure to a single CS2, only disrupts CS2 and leaves CS1 freezing intact. Therefore, it is believed that when the first-order association is directly activated, it is placed into a labile state, which may have an impact on dependent associations. However, when the first-order association is only indirectly activated (through an associative chain), it appears that there is not sufficient stimulation to kick off cellular processes which would place it in a labile state, so it remains fixed.
Clinical applications of such research may be in the areas of PTSD, where victims suffer not only from fearful memories, but also from everyday stimuli somehow associated with the initial trauma. This study shows that disrupting associated reactions will only alleviate the sufferer from these quirky stress reactions, while breaking associative chains at the root cause may provide cascading relief.
The first experiment of the paper used second-order fear conditioning (SOFC) to create an associative memory network in rat brain. To do this, a conditioned stimulus (CS1) is paired with an unconditioned stimulus (US), which naturally elicits a response. After pairing, now CS1 elicits the response (such as freezing in fear). This is the first-order conditioning. Now, a second conditioned stimulus (CS2) is paired with CS1, and by association elicits the response transitively. When extinction of CS1 responding does not affect the responding of CS2, CS2 is considered independent of the first-order fear memory. But if CS2 responding decreases with CS1 extinction, then we have an associative chain (CS2 --> CS1 --> US).
The second experiment, building on such a conditioning chain, discovered that extinction of freezing responses to the first-order stimulus (CS1) leads to responding impairments in CS2. Extinction of the second-order stimulus (CS2), does not have any effect on CS1. This builds a case for a hierarchical, uni-directional chain.
The last experiment examined the effect of activation (memory retrieval) on such an associative chain. (In another paper, Nader and LeDoux showed that reactivation of a memory places it in a labile state -- that is, susceptible to disruption -- until again reconsolidated.) Results demonstrated that protein synthesis inhibition after exposure to a single CS1 impairs responses to both CS1 and CS2. But protein synthesis inhibition after exposure to a single CS2, only disrupts CS2 and leaves CS1 freezing intact. Therefore, it is believed that when the first-order association is directly activated, it is placed into a labile state, which may have an impact on dependent associations. However, when the first-order association is only indirectly activated (through an associative chain), it appears that there is not sufficient stimulation to kick off cellular processes which would place it in a labile state, so it remains fixed.
Clinical applications of such research may be in the areas of PTSD, where victims suffer not only from fearful memories, but also from everyday stimuli somehow associated with the initial trauma. This study shows that disrupting associated reactions will only alleviate the sufferer from these quirky stress reactions, while breaking associative chains at the root cause may provide cascading relief.
Visual Attention
Kanwisher, N. & Wojciulik, E. (November 2000). Visual Attention: Insights from Brain Imaging. Nature Reviews: Neuroscience, Volume 1, 91-98.
This review discusses four major questions related to attention's role in visual processing. First, where in the visual pathway does attention act? Second, what is able to be selected by attention? Third, how does attention affect neural responses? And fourth, where do attentional signals comes from?
Where in the visual pathway does attention act? It has been known for some time that substantial effects of attention can be found in the extrastriate cortex. However, it was not until recently that attentional modulation was discovered in earlier stages of the visual processing pathway (e.g. primary visual cortex). This may be more common when the processing load is considered high.
What gets selected by attention? Under different conditions, attention can select spatial locations, feature dimensions, whole visual objects, or even a combination thereof. However, these may not always be deployed with perfect control.
How does attention affect neural responses? Evidence exists which supports attention influence as being characterized as multiplicative (gain modulations) and/or additive (baseline shifts). And some postulate that increasing baseline activity in a neural population may bring these cells into a dynamic range where the same stimulus input will produce larger responses.
What is the source of attentional signals? Researchers have implicated the fronto-parietal network in providing top-down biasing signals to visual regions, and speculate that this system supports a very heterogeneous set of attention tasks.
This review discusses four major questions related to attention's role in visual processing. First, where in the visual pathway does attention act? Second, what is able to be selected by attention? Third, how does attention affect neural responses? And fourth, where do attentional signals comes from?
Where in the visual pathway does attention act? It has been known for some time that substantial effects of attention can be found in the extrastriate cortex. However, it was not until recently that attentional modulation was discovered in earlier stages of the visual processing pathway (e.g. primary visual cortex). This may be more common when the processing load is considered high.
What gets selected by attention? Under different conditions, attention can select spatial locations, feature dimensions, whole visual objects, or even a combination thereof. However, these may not always be deployed with perfect control.
How does attention affect neural responses? Evidence exists which supports attention influence as being characterized as multiplicative (gain modulations) and/or additive (baseline shifts). And some postulate that increasing baseline activity in a neural population may bring these cells into a dynamic range where the same stimulus input will produce larger responses.
What is the source of attentional signals? Researchers have implicated the fronto-parietal network in providing top-down biasing signals to visual regions, and speculate that this system supports a very heterogeneous set of attention tasks.
Friday, February 15, 2008
Subcortical Face Processing
Johnson, M.H. (October 2005). Subcortical Face Processing. Nature Neuroscience Reviews, Volume 6, 766-774.
The most well-known visual pathway uses parvocellular channels from the retina to the LGN and on to the primary visual cortex, where very complicated fine-grained image processing is carried out. However, evidence supports multiple visual pathways, and last I checked, 12 different visual pathways have been identified in the brain so far. This review paper discusses a specific subcortical face-detection system which involves the superior colliculus, pulvinar, and amygdala.
Researchers hypothesize that this pathway is more rapid than cortical routes, relies on rather low-fidelity (low-spatial-frequency) visual information, and can critically modulate cortical processing. One characterization is that this pathway is important for directing emotional attention, providing an emotional flavoring to higher-order visual processing. As this pathway is thought to bias the cortical processing of visual input -- detecting the prescence of faces, orienting us towards them, and activating dependent cortical regions -- this may a particularly important pathway during development when cortical structures (such as the fusiform face area, orbitofrontal cortices, and other cortical regions involved in the social brain network) are still being molded. Atypical processing of socially salient stimuli, seen in such disorders as autism, Turner syndrome, and Williams syndrome, may be associated with a failures in this subcortical pathways, leading to improper development and specialization of dependent cortical circuits.
The most well-known visual pathway uses parvocellular channels from the retina to the LGN and on to the primary visual cortex, where very complicated fine-grained image processing is carried out. However, evidence supports multiple visual pathways, and last I checked, 12 different visual pathways have been identified in the brain so far. This review paper discusses a specific subcortical face-detection system which involves the superior colliculus, pulvinar, and amygdala.
Researchers hypothesize that this pathway is more rapid than cortical routes, relies on rather low-fidelity (low-spatial-frequency) visual information, and can critically modulate cortical processing. One characterization is that this pathway is important for directing emotional attention, providing an emotional flavoring to higher-order visual processing. As this pathway is thought to bias the cortical processing of visual input -- detecting the prescence of faces, orienting us towards them, and activating dependent cortical regions -- this may a particularly important pathway during development when cortical structures (such as the fusiform face area, orbitofrontal cortices, and other cortical regions involved in the social brain network) are still being molded. Atypical processing of socially salient stimuli, seen in such disorders as autism, Turner syndrome, and Williams syndrome, may be associated with a failures in this subcortical pathways, leading to improper development and specialization of dependent cortical circuits.
Wednesday, February 13, 2008
Differential processing of objects under various viewing conditions in the human LOC
Grill-Spector, K. et al. (September 1999). Differential processing of objects under various viewing conditions in the human lateral occipital complex. Neuron, Vol. 24, 187-203.
This study used fMRIa techniques to investigate the brain's object-selective regions (namely the lateral occipital complex). fMRIa assumes that a group of neurons will respond to repeated presentations of a stimulus with attenuated responses. This signal reduction is presumably the result of neural fatigue from repeated exposure. Thus, "adaptation" data can be used to identify which types of stimulus are effectively treated identically by a certain region of the brain. This is especially interesting in structures further up the processing hierarchy where lower-level transformations have likely given way to more abstract, general representations of the stimuli. Researchers can then explore what properties of objects are preserved and which are transformed to a canonical representation by the time signals converge on a specific region.
First, the study sought to understand how long adaptation effects last. Time durations as long as 8 sec between matched stimuli still elicited amplitude reductions, establishing that adaptation has a fairly long-lasting effect.
Secondly, the study set out to examine which object properties were invariant within the LOC. The results indicate that the LOC is less sensitive to changes in size and position, compared to changes induced by illumination and viewpoint (rotation). In other words, it seems the LOC receives visual input which has been normalized for size and position.
This study used fMRIa techniques to investigate the brain's object-selective regions (namely the lateral occipital complex). fMRIa assumes that a group of neurons will respond to repeated presentations of a stimulus with attenuated responses. This signal reduction is presumably the result of neural fatigue from repeated exposure. Thus, "adaptation" data can be used to identify which types of stimulus are effectively treated identically by a certain region of the brain. This is especially interesting in structures further up the processing hierarchy where lower-level transformations have likely given way to more abstract, general representations of the stimuli. Researchers can then explore what properties of objects are preserved and which are transformed to a canonical representation by the time signals converge on a specific region.
First, the study sought to understand how long adaptation effects last. Time durations as long as 8 sec between matched stimuli still elicited amplitude reductions, establishing that adaptation has a fairly long-lasting effect.
Secondly, the study set out to examine which object properties were invariant within the LOC. The results indicate that the LOC is less sensitive to changes in size and position, compared to changes induced by illumination and viewpoint (rotation). In other words, it seems the LOC receives visual input which has been normalized for size and position.
fMRIa
Krekelberg, B, Boynton, G.M., & van Wezel, R.J.A. (2006). Adaptation: from single cells to BOLD signals. Trends in Neuroscience.
Functional magnetic resonance imaging adaptation (fMRIa) is an increasingly popular method which takes advantage of the brain changes which occur in response to long exposure to some evocative stimulus. If Stimulus 1 (S1) excites a certain neuronal population, repeated exposure to S1 will result in subsequently attenuated responses. This may be due to neural fatigue (i.e. the more a neuron fires, the more its subsequent responses will be reduced) or may be due to coupled hemodynamic processes. However, when S1 is followed by a unique stimulus, S2, the response amplitudes should not be attenuated as a fresh sub-population of neurons is excited. Using this technique can allow researchers to determine if the same or unique neuronal groups are involved in processing two stimuli. This paper goes on to describe the utility of the technique in examination of the visual system, particularly orientation, motion, and face detection. It also stresses the importance of adaptation timescale in experimental design.
Functional magnetic resonance imaging adaptation (fMRIa) is an increasingly popular method which takes advantage of the brain changes which occur in response to long exposure to some evocative stimulus. If Stimulus 1 (S1) excites a certain neuronal population, repeated exposure to S1 will result in subsequently attenuated responses. This may be due to neural fatigue (i.e. the more a neuron fires, the more its subsequent responses will be reduced) or may be due to coupled hemodynamic processes. However, when S1 is followed by a unique stimulus, S2, the response amplitudes should not be attenuated as a fresh sub-population of neurons is excited. Using this technique can allow researchers to determine if the same or unique neuronal groups are involved in processing two stimuli. This paper goes on to describe the utility of the technique in examination of the visual system, particularly orientation, motion, and face detection. It also stresses the importance of adaptation timescale in experimental design.
Tuesday, February 12, 2008
Neuronal CPEB Stabilizes Synapse-Specific LTF
Si, K. et al. (December 26, 2003). A neuronal isoform of CPEB Regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in Aplysia. Cell, Vol. 115, 893-904.
Synaptic plasticity has been offered as one answer to questions regarding the neurobiological mechanisms of memory. The gist of plasticity is that the synapses are effectively "strengthened", forming a stronger connection between neighboring neurons. Plasticity has at least two forms: one a short-term form lasting minutes, and the other a long-term form lasting days or weeks. How does each work? And how are specific, individual synapses strengthened when most cellular mechanisms (e.g. gene expression) are thought to act cell-wide?
Short-term changes are characterized by covalent modifications of preexisting proteins and the strengthening of preexisting connections. However, specific mechanisms for this are not offered by the authors. This paper takes aim instead at long-term plasticity, characterized by creation and projection of of new synaptic connections and growth of new synaptic terminals, requiring both structural changes in the shape, size, and morphology of the synapse as well as regulatory controls that determine where and when to grow.
The article shows that neural stimulation can: (1) send a signal from the synapse to the nucleus that kicks off the gene expression process necessary for long-term facilitation, and (2) "mark" the specific activated synapse so that translation can occur (proper materials can be synthesized) at the specifically marked synapse. CPEB, which resembles a prion (a protein that can switch between two functionally distinct morphological states), seems to act as the needed "marker". ApCPEB appears necessary for the long-term stabilization of facilitation, but not for short-term facilitation. Its ability to polyadenylate (elongate) the mRNA that reaches the marked synapse stabilizes this mRNA molecule, allowing it to resist catalyzation longer thereby increasing its output of building-block proteins. Interestingly, this process can be kicked off by as little as one, single stimulation event.
For a more holistic review of memory mechanisms, see Molecular Mechanisms for Storage.
Synaptic plasticity has been offered as one answer to questions regarding the neurobiological mechanisms of memory. The gist of plasticity is that the synapses are effectively "strengthened", forming a stronger connection between neighboring neurons. Plasticity has at least two forms: one a short-term form lasting minutes, and the other a long-term form lasting days or weeks. How does each work? And how are specific, individual synapses strengthened when most cellular mechanisms (e.g. gene expression) are thought to act cell-wide?
Short-term changes are characterized by covalent modifications of preexisting proteins and the strengthening of preexisting connections. However, specific mechanisms for this are not offered by the authors. This paper takes aim instead at long-term plasticity, characterized by creation and projection of of new synaptic connections and growth of new synaptic terminals, requiring both structural changes in the shape, size, and morphology of the synapse as well as regulatory controls that determine where and when to grow.
The article shows that neural stimulation can: (1) send a signal from the synapse to the nucleus that kicks off the gene expression process necessary for long-term facilitation, and (2) "mark" the specific activated synapse so that translation can occur (proper materials can be synthesized) at the specifically marked synapse. CPEB, which resembles a prion (a protein that can switch between two functionally distinct morphological states), seems to act as the needed "marker". ApCPEB appears necessary for the long-term stabilization of facilitation, but not for short-term facilitation. Its ability to polyadenylate (elongate) the mRNA that reaches the marked synapse stabilizes this mRNA molecule, allowing it to resist catalyzation longer thereby increasing its output of building-block proteins. Interestingly, this process can be kicked off by as little as one, single stimulation event.
For a more holistic review of memory mechanisms, see Molecular Mechanisms for Storage.
Sunday, February 10, 2008
Retinotopy and Functional Subdivision of Human Areas MT and MST
Huk, A.C. et al. (August 15, 2002). Retinotopy and Functional Subdivision of Human Areas MT and MST. The Journal of Neuroscience, Volume 22, Number 16, 7195-7205.
Much research in neuroscience has begun with animal studies (and invasive techniques) and only later been continued with human subjects (with predominantly non-invasive methodologies). This paper discusses the attempts to reconcile the areas of visual cortex responsible for detecting visual motion in the macaque and the human. In particular, two sub-divisions of the dorsal superior temporal sulcus (STS) are well-studied in the macaque: the middle temporal (MT) and the medial superior temporal (MST) visual areas. The MT is characterized by a distinguishable retinotopic map and a coarse-grained small receptive field, whereas the MST is just the opposite. This experiment was designed to recognize areas displaying these characteristics in the human MT+ or V5 area, thought to be homologous to the macaque STS, using fMRI. Subregions of the human MT+ were tentatively identified, bridging the gap between animal and human research.
Much research in neuroscience has begun with animal studies (and invasive techniques) and only later been continued with human subjects (with predominantly non-invasive methodologies). This paper discusses the attempts to reconcile the areas of visual cortex responsible for detecting visual motion in the macaque and the human. In particular, two sub-divisions of the dorsal superior temporal sulcus (STS) are well-studied in the macaque: the middle temporal (MT) and the medial superior temporal (MST) visual areas. The MT is characterized by a distinguishable retinotopic map and a coarse-grained small receptive field, whereas the MST is just the opposite. This experiment was designed to recognize areas displaying these characteristics in the human MT+ or V5 area, thought to be homologous to the macaque STS, using fMRI. Subregions of the human MT+ were tentatively identified, bridging the gap between animal and human research.
New images from human visual cortex
R.B.h. Tootell et al. (1996). New images from human visual cortex. Trends in Neuroscience, Vol. 19, No. 11, 481-489.
This article takes aim at broadly reviewing animal and human studies of the human visual cortex. There has been a long and successful tradition of studying the visual cortex in our Old World monkey relatives, the macaques. Although there are significant differences, there are also striking similarities and key learnings that can be generalized from examination of macaque cortex. The article discusses the attempts to converge the research in these two different disciplines of human and animal studies on the basis of functional properties, retinotopy, histology, and connectivity. Among others, it covers the principles of disproportionate cortical mapping, cortical flattening (or unfolding) techniques common to animal studies, and the 'where' vs. 'what' pathways of the visual system. Although these two distinct pathways are well understood in the monkey, they are defined with more uncertainty in the human. The article discusses motion processing and spatial organization in the dorsal 'where' pathway, and color processing, form recognition, and object identification in the ventral 'what' pathway.
This article takes aim at broadly reviewing animal and human studies of the human visual cortex. There has been a long and successful tradition of studying the visual cortex in our Old World monkey relatives, the macaques. Although there are significant differences, there are also striking similarities and key learnings that can be generalized from examination of macaque cortex. The article discusses the attempts to converge the research in these two different disciplines of human and animal studies on the basis of functional properties, retinotopy, histology, and connectivity. Among others, it covers the principles of disproportionate cortical mapping, cortical flattening (or unfolding) techniques common to animal studies, and the 'where' vs. 'what' pathways of the visual system. Although these two distinct pathways are well understood in the monkey, they are defined with more uncertainty in the human. The article discusses motion processing and spatial organization in the dorsal 'where' pathway, and color processing, form recognition, and object identification in the ventral 'what' pathway.
Wednesday, February 6, 2008
A flexible fusiform area for subordinate-level visual processing automatized by expertise
Tarr, M.J. & Gauthier, I. (August 2000). FFA: A flexible fusiform area for subordinate-level visual processing automatized by expertise. Nature Neuroscience, Volume 3, Number 8, 764-769.
The article explores the controversy over face perception in the fusiform gyrus. Is face perception carried out by domain-specific mechanisms specialized for processing faces in particular, or are faces handled by domain-general mechanisms? This article argues for the latter alternative. Specifically, it emphasizes categorization and expertise in a given object domain (e.g. faces, cars) affect the response of the fusiform area independent of stimulus geometry. Counter-evidence and rebuttals are too complicated to get into in such a summary. However, the heatedness of the debate leaves this issue far from closed.
The article explores the controversy over face perception in the fusiform gyrus. Is face perception carried out by domain-specific mechanisms specialized for processing faces in particular, or are faces handled by domain-general mechanisms? This article argues for the latter alternative. Specifically, it emphasizes categorization and expertise in a given object domain (e.g. faces, cars) affect the response of the fusiform area independent of stimulus geometry. Counter-evidence and rebuttals are too complicated to get into in such a summary. However, the heatedness of the debate leaves this issue far from closed.
Domain specificity in face perception
Kanwisher, N. (August 2000). Domain specificity in face perception. Nature Neuroscience, Volume 3, Number 8, 759-763.
The article explores the controversy over face perception in the fusiform gyrus. Is face perception carried out by domain-specific mechanisms specialized for processing faces in particular, or are faces handled by domain-general mechanisms? This article argues for the former alternative. It uses inversion, holistic recognition advantages, and a double-dissociation between face and object recognition found in the neuropsychological record (prosopagnosia patients who cannot recognize faces but who can recognize objects and C.K. who is impaired in reading and object recognition but whose facial recognition is preserved) as primary pieces of evidence. Counter-evidence and rebuttals are too complicated to get into in such a summary. However, the case seems far from closed.
The article explores the controversy over face perception in the fusiform gyrus. Is face perception carried out by domain-specific mechanisms specialized for processing faces in particular, or are faces handled by domain-general mechanisms? This article argues for the former alternative. It uses inversion, holistic recognition advantages, and a double-dissociation between face and object recognition found in the neuropsychological record (prosopagnosia patients who cannot recognize faces but who can recognize objects and C.K. who is impaired in reading and object recognition but whose facial recognition is preserved) as primary pieces of evidence. Counter-evidence and rebuttals are too complicated to get into in such a summary. However, the case seems far from closed.
Monday, February 4, 2008
Serotonin and Hallucinogens
Aghajanian, G.K. & Marek, G.J. (1999). Serotonin and Hallucinogens. Neuropsychopharamcology, Vol. 21, No. 2S.
Many possibilities are offered as to how LSD and other hallucinogens create their unusual psychoactive effects. The article gets very specific with different serotonin sub-types in different brain regions being implicated. I find the article and the facts confusing enough to assume that the complicated effect enacted in the use of such psychedelics will be only be fully understood after considerably more research.
Many possibilities are offered as to how LSD and other hallucinogens create their unusual psychoactive effects. The article gets very specific with different serotonin sub-types in different brain regions being implicated. I find the article and the facts confusing enough to assume that the complicated effect enacted in the use of such psychedelics will be only be fully understood after considerably more research.
Sunday, February 3, 2008
Psychedelic Medicine
Horgan, J. (February 26, 2005). Psychedelic Medicine: Mind bending, health giving. New Scientist.
A typical overview of the tumultuous history of the use of psychedelics in medicine and therapy by science writer John Horgan. I found the 'Psychedelic Healing' more interesting and informative; I would recommend reading this instead.
A typical overview of the tumultuous history of the use of psychedelics in medicine and therapy by science writer John Horgan. I found the 'Psychedelic Healing' more interesting and informative; I would recommend reading this instead.
Friday, February 1, 2008
Autonomic Correlates of ADHD and ODD in Preschool Children
Cromwell, S.E., Beauchaine, T.P., Gatzke-Kopp, L., Sylvers, P., Mead, H., & Chipman-Chacon, J. (2006). Autonomic Correlates of Attention-Defecit/Hyperactivity Disorder and Oppositional Defiant Disorder in Preschool Children. Journal of Abnormal Psychology, Volume 115, Number 1, 174-178.
Conduct disorder in adolescence and antisocial behavior in adults has been shown to be marked by autonomic underarousal. This study attempted to see if much younger, at-risk pre-schoolers are autonomically similar to older externalizing children and adults. Firstly, the study found that pre-school children with ADHD and ODD showed attenuated EDR, a measure of sympathetic nervous system (SNS). Decreased SNS activity is thought to be a marker of disinhibition. Secondly, the study found ADHD and ODD pre-schoolers have attenuated SNS-linked cardiac activity, which serves as a marker of reward sensitivity. Children with underactive reward systems may engage in reward-seeking behavior to compensate for a chronically suppressed dopaminergic subsystem. Finally, as compared with controls, the paper showed no substantial differences in these ADHD/ODD groups in RSA, a marker of parasympathetic nervous system (PNS) activity, and more generally, emotional regulation. The results support the hypothesis that even very young ADHD and ODD children are similar in autonomic biology to older antisocial groups. However, these preschool years may represent a critical period during which noradrenergic, serotonergic, and dopaminergic systems that govern behavioral control are most vulnerable to long-term changes, and importantly, emotional dysregulation, a hallmark of most psychological disorders, may be positively affected through early detection and intervention during this timeframe.
Conduct disorder in adolescence and antisocial behavior in adults has been shown to be marked by autonomic underarousal. This study attempted to see if much younger, at-risk pre-schoolers are autonomically similar to older externalizing children and adults. Firstly, the study found that pre-school children with ADHD and ODD showed attenuated EDR, a measure of sympathetic nervous system (SNS). Decreased SNS activity is thought to be a marker of disinhibition. Secondly, the study found ADHD and ODD pre-schoolers have attenuated SNS-linked cardiac activity, which serves as a marker of reward sensitivity. Children with underactive reward systems may engage in reward-seeking behavior to compensate for a chronically suppressed dopaminergic subsystem. Finally, as compared with controls, the paper showed no substantial differences in these ADHD/ODD groups in RSA, a marker of parasympathetic nervous system (PNS) activity, and more generally, emotional regulation. The results support the hypothesis that even very young ADHD and ODD children are similar in autonomic biology to older antisocial groups. However, these preschool years may represent a critical period during which noradrenergic, serotonergic, and dopaminergic systems that govern behavioral control are most vulnerable to long-term changes, and importantly, emotional dysregulation, a hallmark of most psychological disorders, may be positively affected through early detection and intervention during this timeframe.
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