Shared Neural Circuits for Mentalizing about the Self and Others.

Lombardo MV, Chakrabarti B, Bullmore ET, Wheelwright SJ, Sadek SA, Suckling J, Baron-Cohen S.

University of Cambridge, United Kingdom.

Abstract Although many examples exist for shared neural representations of self and other, it is unknown how such shared representations interact with the rest of the brain. Furthermore, do high-level inference-based shared mentalizing representations interact with lower level embodied/simulation-based shared representations? We used functional neuroimaging (fMRI) and a functional connectivity approach to assess these questions during high-level inference-based mentalizing. Shared mentalizing representations in ventromedial prefrontal cortex, posterior cingulate/precuneus, and TPJ all exhibited identical functional connectivity patterns during mentalizing of both self and other. Connectivity patterns were distributed across low-level embodied neural systems such as the frontal operculum/ventral premotor cortex, the anterior insula, the primary sensorimotor cortex, and the presupplementary motor area. These results demonstrate that identical neural circuits are implementing processes involved in mentalizing of both self and other and that the nature of such processes may be the integration of low-level embodied processes within higher level inference-based mentalizing.

Spreng RN, Grady CL. Spreng RN, Grady CL. Patterns of Brain Activity Supporting Autobiographical Memory, Prospection, and Theory-of-Mind and Their Relationship to the Default Mode Network. J Cogn Neurosci. 2009 Jul 6 The ability to rise above the present environment and reflect upon the past, the future, and the minds of others is a fundamentally defining human feature.

It has been proposed that these three self-referential processes involve a highly interconnected core set of brain structures known as the default mode network (DMN).

The DMN appears to be active when individuals are engaged in stimulus-independent thought.

This network is a likely candidate for supporting multiple processes, but this idea has not been tested directly.

We used fMRI to examine brain activity during autobiographical remembering, prospection, and theory-of-mind reasoning.

Using multivariate analyses, we found a common pattern of neural activation underlying all three processes in the DMN.

In addition, autobiographical remembering and prospection engaged midline DMN structures to a greater degree
and theory-of-mind reasoning engaged lateral DMN areas.

A functional connectivity analysis revealed that activity
of a critical node in the DMN, medial prefrontal cortex,
was correlated with activity in other regions in the DMN during all three tasks.

We conclude that the DMN supports common aspects of these cognitive behaviors involved in simulating an internalized experience

There is reasonably good evidence that the cells [ grey matter ] and the connections [ white matter ] are reduced in schizophrenia, so that their brain has to use more connecting to get to the same result as healthier brains, and in complicated situations of connection and retrieval of context, the connecting is not enough, is not active enough, or goes astray.

Bratislava:- Resting state default mode network can be reliably traced using fMRI. The integrity of the network has functional consequences. 9 healthy subjects performed non-trivial sequencing task during fMRI. Deactivation during the active paradigm revealed the default mode network. Nodes of this network play a role in the neurobiology of schizophrenia. Therefore the method is usefull for the schizophrenia research.

Yong Liu; Meng Liang; Yuan Zhou; Yong He; Yihui Hao; Ming Song; Chunshui Yu; Haihong Liu; Zhening Liu; Tianzi Jiang

findings demonstrated that the brain functional networks had efficient small-world properties in the healthy subjects; whereas these properties were disrupted in the patients with schizophrenia. Brain functional networks have efficient small-world properties which support efficient parallel information transfer at a relatively low cost. More importantly, in patients with schizophrenia the small-world topological properties are significantly altered in many brain regions in the prefrontal, parietal and temporal lobes. These findings are consistent with a hypothesis of dysfunctional integration of the brain in this illness. Specifically, we found that these altered topological measurements correlate with illness duration in schizophrenia.

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Robert Freedman, M.D. How the mind loses its way in schizophrenia has puzzled psychiatrists since the syndrome was first described in the 19th century. Nearly every advance in experimental psychology has included attempts to describe hallucinations and delusions as deficits in specific steps of thinking in schizophrenia.

Persons with schizophrenia often cannot automatically discriminate important from unimportant information. Gur et al. (Figure 1) tested whether the problem is the patients’ inability to select what they respond to (top-down processing) or whether it is caused by their inability to filter out responses to distracting stimuli (bottom-up processing). The subjects watched a screen for target symbols that required them to push a button while intermittent distracting pictures were also presented. Gur et al. found decreased blood flow in the frontal cortex and basal ganglia to the target stimuli in schizophrenia. This evidence, acquired using functional magnetic resonance imaging (fMRI), indicates that the brain is not as active in selecting stimuli in the frontal cortex for responses programmed by the basal ganglia. However, the distractor stimuli overactivated the blood flow in the inferior parietal lobe, indicating that neurons there were not as able to discriminate the distractors from the more important target stimuli. Thus, persons with schizophrenia have both problems in information processing.

The brain idles in a default mode in which there is interconnected processing of activity among major centers in the cerebral cortex. Garrity et al. (Figure 2) studied this default activity with auditory stimuli, both targets and distractors. They studied the activity of an interconnected network that includes the frontal, cingulate, parietal, and parahippocampal cortices. Although in normal comparison subjects, the network, as measured by its blood flow with fMRI, resonates slowly and regularly, in schizophrenia the activity is increased and more irregular and also correlates with positive symptoms. Garrity et al. conclude that the brain in schizophrenia is, within some portions, hyperactive and some parts hypoactive, but the entire circuit is unable to stabilize itself in the default mode.

Ferrarelli et al. (Figure 3) examined spontaneous brain activity when schizophrenia patients were asleep, thereby avoiding issues of reduced motivation and increased distractibility. By using a 256-channel EEG system, they found a specific deficit in sleep spindles—waxing and waning oscillations at around 12–15 cycles per second that occur over the central and parietal brain areas. Sleep spindles are generated by the thalamic reticular nucleus, a thin sheet of inhibitory neurons interposed between the thalamus and the cortex that would appear to be hypoactive in schizophrenia, even during sleep. Dysfunction of this nucleus has implication for the waking state, when it plays an important role in sensory gating and attentional modulation, functions that are impaired in schizophrenia.

Inhibition is also the theme of the demonstration by Ford et al. (Figure 4) of brain electrical activity before and during speech. Activity in the cortex becomes highly synchronized about 150 msec before the patient says "ah." The "ah" itself results in activity, measured as the N1 wave of an auditory evoked potential. If the "ah" is generated by the patient’s speech, then the N1 is reduced. Ford et al. suggest that the preparation for speech activates inhibitory neurons in the cerebral cortex. The diminished N1 demonstrates that the activity of the cortex is inhibited, and this inhibition helps normal persons distinguish their own speech from others. Ford et al. hypothesize that malfunction of this system, demonstrated as failure of prespeech synchronization and the lack of inhibition of N1, results in failure of the persons with schizophrenia to distinguish their speech from that of others.

Shergill et al. (Figure 5) use diffusion tensor imaging, a magnetic resonance technique that assesses the alignment of water molecules in myelin fiber paths (fractional anisotropy) as a measure of the integrity of the connections between neuronal areas. One finding is an overall decrease in schizophrenia, in relation to normal comparison subjects, of the myelin pathway between Broca’s motor speech area in the frontal lobe and Wernicke’s receptive speech area in the temporal lobe. Within the schizophrenia group, however, the pathway is closest to normal in patients who have active auditory hallucinations.

Leitman et al. (Figure 6) also use diffusion tensor imaging to evaluate connections between brain regions—in this case, to determine why patients with schizophrenia have difficulty in evaluating other people’s emotions based upon the rhythm and tone of speech, termed "prosody." The patients showed deficits not only in differentiating emotions, such as happiness versus sadness, but also in determining whether a common tune was played correctly or with altered notes. An inability to detect both emotions and incorrect tunes was related to a decrease in the integrity in the connections to the auditory cortex ("acoustic radiations"), indicating that the same types of "disconnections" that occur elsewhere in the brain occur also within simple sensory systems. In a follow-up study, Leitman et al. found that patients also had difficulty in differentiating questions versus statements based upon tone of voice alone, suggesting that deficits in the ability to detect prosody may interfere generally with the patients’ ability to interact socially.

Bleuler was among the first to point out that persons with schizophrenia are unusually aware of stimuli in their surroundings, which he ascribed to failure in an unknown inhibitory brain mechanism.
Three studies reaffirm Bleuler’s initial observation that deficits in schizophrenia include problems in processing stimuli at the most basic levels:
the failure to inhibit activation by distractors in the study by Gur et al.,
the failure to maintain stable default processing in the study by Garrity et al.,
and the failure of the inhibitory thalamic reticular nucleus to function even during sleep in the study by Ferrarelli et al. When we consider more complex psychological processes—discerning internal from external speech, as in the study by Ford et al.:the same sorts of elementary inhibitory processes seem to be involved.

The conclusion is similar with EEG analysis, recently enhanced by dense multiple channel recording and new analytic techniques, and the measurement of changes in blood flow with fMRI.
Blood flow in the brain changes very precisely in time and space in relation to neuronal activity.
The magnetic resonance imager measures the new inflow of oxygenated hemoglobin by the change in the quantum state of the iron molecule inside the heme moiety.
The two fMRI studies use a signal detection task that originally demonstrated abnormalities in schizophrenia over 30 years ago.
The fMRI technique confirms that there is an abnormality in brain function elicited by the task
and shows that it is a complex abnormality involving abnormal activation and inhibition in many brain regions.

Two studies use the magnetic resonance imager in the diffusion tensor imaging mode to look at myelin integrity.
The finding of alteration in white matter complements earlier findings of reduced gray matter in schizophrenia.

The finding of Shergill et al. that temporal-frontal pathways are relatively preserved in patients with auditory hallucinations
is evidence that the strengths left to persons with schizophrenia sometimes exacerbate the signs of their illness.
More intelligent patients have long been known to have more difficult and persistent paranoia.

Here a more intact auditory system ends up to be the substrate of increased auditory hallucinations.

Leitman et al. examine a wide range of abnormalities, from executive function to tone detection,
and find that all of them are correlated with white matter problems in their appropriate areas,
from the primary auditory cortex to the prefrontal lobes.

Thus, different psychological abnormalities may have a similar type of tissue pathology,
with the difference in psychological outcome simply reflecting the area of the brain involved.

The parsing of schizophrenia neuropsychologically then becomes similar to the neurologist’s evaluation of a stroke:
the vascular process is the same, but the consequence to the patient depends on which brain region is infarcted.

All six studies examined patients taking medication, and it is fair to ask if we are seeing pathology that is not corrected by medication or whether we are seeing the effects of medication.
The authors make reasonable cases that uncorrected pathology, rather than medication effect, is the likely source of their findings.
If so, the studies reaffirm to us the burden of illness that patients face in trying to approach even very simple tasks.
Gur et al., for example, point out that distractors cause much larger areas of the frontal cortex
to become activated in schizophrenia than in healthy comparison subjects.
One explanation is that the patients, who ultimately perform as well as the comparison subjects on these simple tasks,
must expend much more effort at higher executive brain levels
to handle tasks that are handled more easily and automatically at lower sensory levels by the comparison subjects.

It is sometimes helpful to tell patients something about how their brains may be malfunctioning. For example, one of my patients was in trouble with his family because he spent too much time with an audio synthesizer that produced ocean noises.

I explained to him and his family that his control over the wave noises
was substituting for his inability to control the noisy environment in his apartment house.

They linked the use of the synthesizer to his becoming ill, whereas I saw it as his attempt at restoration.

Together, he and his family reached an understanding
of when he needed to use the wave sounds by himself
and when he should attempt to interact with his family instead of relying on it to isolate himself.

Uncertainty For example, the ability to remember facts and events, referred to as declarative memory, relies on an intact hippocampus in humans.

The ability to learn relationships between items is an essential property of human intelligence.

For example, having learned in panel A of the figure that A geater than B and B greater than C, we can infer from these two relationships that A is greater than C.

This ability is referred to in relational memory as transitive inference.
Specific functions of relational memory, such as transitive inference, are impaired in psychiatric patients, while other aspects of declarative memory remain intact

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The human brain operates on two levels at the same time: one in contact with reality, the other focused on internally generated "mental images" (when dreaming, internal images are "unopposed"). Whether this "dual processing" is related to the lateralization of the brain (i.e., two brains working somewhat independently) or to the enlargement of the frontal lobes (both relatively unique features of the human brain) or both is unclear. In schizophrenia, the relationships between internally derived perceptions and outside reality are out of balance; internally derived perceptions are excessively strong (and seem to be external). This conceptualization can explain both positive and negative symptoms. Positive symptoms are because of internally derived perceptions being stronger than usual. Negative symptoms are more attributable to the "weakness" of focus on external reality. Schizophrenia patients are less concerned with how they look, smell, and interact with others, with accomplishments in the real world, and with whether others understand them. They are more concerned with internally derived perceptions. If the complex mechanism that creates mental images malfunctions, can one measure it? Is the size of the frontal lobe, or blood flow, or levels of dopamine, or an evoked potential, going to tell us much about the relative strength of the mental images? Probably not, since the creation and manipulation of mental images probably involve much of the brain and innumerable neurotransmitters, receptors, and connections. It may be that our complex technologies, although impressive, are still unlikely to clarify the malfunction that causes schizophrenia.

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nhibition problems might also underlie the difficulties that schizophrenic patients have in settling into the healthy "idle" brain mode seen in normal individuals. Using fMRI, Garrity et al. found that when at rest, a network involving the frontal, cingulate, and parahippocampal cortices in schizophrenia patients exhibited irregular timing — not the regular, slow resonance seen in healthy people. Positive symptoms correlated with abnormal medial frontal, temporal, and cingulate activity. The thalamic reticular nucleus is a thin sheet of inhibitory neurons between the thalamus and cortex, which generates sleep spindles and which appears to be hypoactive in schizophrenia. Ferrarelli et al. used a 256-channel EEG during sleep. In sleep spindles at 12 to 15 cycles per second, they found a specific deficit in schizophrenic subjects, compared with both healthy controls and patients with depression histories. Similarly, Ford et al., in a study of auditory-evoked potentials, demonstrated that schizophrenic patients had poor inhibition of certain cortical areas, which normally occurs when preparing for speech. The authors postulate that this lack of inhibition contributes to patients’ difficulties in distinguishing others’ speech from their own. Diffusion tensor imaging assesses the integrity of white matter by examining how water molecules align in myelin. Using this technique, Shergill et al. found that patients had an overall reduction in myelin pathways between the Broca and Wernicke areas (i.e., the frontal-lobe region that controls motor speech and the temporal-lobe region that controls receptive speech, respectively). Curiously, the pathways were closest to normal in patients with active auditory hallucinations. Also using diffusion tensor imaging, Leitman et al. found deficient integrity in the connections to the auditory cortex ("acoustic radiation"). These decrements correlated with patients’ difficulties in using tone of voice to identify emotions and sentence type (question vs. statement) and even in determining whether common tunes were played with the correct notes. These findings may account for patients’ difficulties in evaluating other people’s emotions. Comment: Over the decades, numerous neuropsychological difficulties have been described in patients with schizophrenia. What we call schizophrenia is a diverse group of syndromes that affect different patients in sundry ways. If all of these researchers had studied the same patients, we might have learned the extent to which this astounding array of deficits occurs concurrently and how specific phenomenologic features correlate with specific biologic findings. An editorialist who attempts to make sense of this dizzying diversity of findings points out that all of the authors make good cases that their findings are due to uncorrected pathology rather than to medication effects. He hypothesizes that a single underlying pathology might affect different brain regions, as occurs in stroke patients. If so, clinical differences among patients might indicate individual variation in brain areas vulnerable to these underlying processes. Researchers could test this interesting idea by searching for more-fundamental common processes, e.g., whether these various neuroimpairments are associated with specific brain protein abnormalities.

Footnotes

Greater hippocampal-midbrain engagement during integrative encoding enables rapid behavioral generalization in the future

By forming a thread that connects otherwise separate experiences,
integrative encoding permits organisms to generalize across multiple past experience to guide choices in the present, explains Dr. Shohamy.
Areas of the brain that were predictive of generalization ability were the hippocampus; the ventral tegmental area (VTA), and substantia nigra in the midbrain.<

For the poor learners there is no role for the hippocampus or the VTA,
“n people who generalize successfully, the brain is constantly building links across separate events, at the time of those events

creating an integrated memory of life’s episodes.

For others, although the brain may accurately remember each past event, this integration does not occur,
so that when confronted with a new situation,
they are unable to flexibly apply what they learned in the past

The basal ganglia are necessary for learning a new response
when a previously learned response is no longer rewarding.
Studies implicate the basal ganglia in incremental, feedback-based learning that involves integrating information across multiple experiences

The failure of the hippocampal amnesic subjects
to reverse their response or to learn a new cue
is consistent with a more general role for the hippocampus in configural learning,
and suggests it may also support
the ability to respond to changes in cue-outcome contingencies

 

The medial temporal lobes, by contrast, contribute to rapid encoding of relations between stimuli now

In psychiatric disorders you do not have a broken memory, but a system that has lost fidelity and is not as accurate anymore.

In this regard it is relevant that those subjects who did generalize well had no idea that they were doing so. They appeared to have a memory that they had seen a given face and scene as a pair when in fact they had not.

The researchers used functional MRI (fMRI) to map areas of brain activation in 24 college students undergoing an associative learning and generalization task. The participants were shown pairs of images/faces and scenes - learning to associate the two.
After the learning phase, the students were then asked to link faces and scenes in a test phase.
Since some faces and scenes were paired more than once, the researchers were able to test how well the subjects generalize based on overlap.
For example, if Mary’s face had been paired with scenes of an oak tree and a sunset, but John’s face had been only paired with the oak tree,
then would the subjects generalize at test phase by linking John’s face with the sunset scene as well?
That is, in fact, what the researchers found.
But it was not so much that the subjects were able to generalize in this manner,
but what goes on in the brain when they do, that supports the “integrative encoding” hypothesis.

If generalization is to be explained by the alternative logical inference” model - where memories are retrieved and analyzed on the spot
then it should correlate with activation of the brain areas involved in the process.
However, Shohamy and Wagner found no link between hippocampal activation and performance in the generalization part of the tests.
That suggests that there is no additional retrieval process going on during generalization.
On the other hand, the researchers did find a correlation between generalization prowess
and hippocampal and midbrain activation during the learning phase.
We found that all the action happened essentially while people were experiencing the individual events, what we call the premise event.
That is when people who later generalize well showed a lot of hippocampal activity.
People who later didn’t generalize well didn’t show this early on, said Shohamy.
The results show that the brain events that predict the behavior
were happening not at the time of generalization but earlier on, at the time of learning.

That was really the key thing,” said Shohamy. Generalization was also much more rapid than might be expected if the logical inference” model held true.

The areas of the brain that were predictive of generalization ability were
the hippocampus and the ventral tegmental area (VTA), and substantia nigra in the midbrain. “That is a relatively novel finding,” suggested Shohamy.

Generally the role of dopamine in learning is thought to be separate from what the hippocampus is doing inputs for procedural learning and habits, exactly the kind of thing that people think is intact in people with Alzheimer disease and hippocampal damage,” said Shohamy.
However, more recent research, including this study, suggests dopaminergic involvement is not so simple and that it may modulate what happens in the hippocampus.
Alison Adcock at Duke University, Durham, North Carolina, for example, has shown that dopaminergic innervation may link motivation with better encoding in the hippocampus (see Adcock et al., 2006 ) and John Lisman at Brandeis University, Waltham, Massachusetts, and Anthony Grace at the University of Pittsburgh, Pennsylvania,
have theorized that VTA and hippocampal neurons form a functional loop (see Lisman and Grace, 2005 ). Exactly how dopaminergic innervation influences hippocampal memory is not clear.
One possibility, posited by Dharshan Kumaran, Wellcome Trust Center for Neuroimaging, London, and Emrah Duzel, University College London, in an accompanying Neuron preview,
is that dopamine alters neuronal plasticity by inducing synaptic proteins.
Since that process would take some time, Kumaran and Duzel suggest that adjusting the interval between presenting the overlapping pairs of visual stimuli might be insightful. “This is pretty exciting work,” said Stephan Heckers, Vanderbilt University, Tennessee, in an interview with ARF. Heckers also studies learning and memory in humans and previously showed that generalization is related to activation of the hippocampus (Heckers et al., 2004 ). “The relationship between the hippocampus and the ventral tegmental area is not entirely novel, but what they have shown is that it takes place at the time of encoding. That is novel, and this might be the first study that supports the Lisman and Grace model,” he said.
Heckers also found that in cued-recall tests
only two areas of the brain predict accuracy, the hippocampus and the VTA, and he has seen other links between the VTA and memory.
Now I’m intrigued, because we have seen something similar not only during encoding but also during the retrieval phase, he said.

Could this interplay between the dopaminergic system and the hippocampus explain, even partly, cognitive dysfunction in Parkinson disease or even affect cognition in AD? Shohamy said it is not so clear. “It is complicated. Midbrain dopamine modulates several different systems,” she said. The striatum, for example, has received a lot of attention, and there has been some work linking it to cognition in PD, but in this study
Shohamy found no correlation between generalizability and the striatum. Also, in collaboration with colleagues at Rutgers, Shohamy previously reported that while PD patients have trouble learning episodes, once they do, they have no trouble generalizing (see Shohamy et al., 2006 ). Heckers is also not sure how this work might relate to AD, PD, or other cognitive deficit conditions. “For people who are primarily presenting with cognitive deficits, such as dementia, or cognitive deficits in Parkinson disease, I do not know how much this particular experiment explains it, because they show these nice relationships between behavior and brain activation only for the good learners who make generalizations. For the poor learners there is no role for the hippocampus or the VTA, so it does not really give us clues about what is not working in a patient who has cognitive deficit,” he said. In fact, Shohamy is interested in studying how good versus poor generalizability may affect daily life.
I think the notion of generalizability is interesting. On one hand you can imagine that it is a powerful thing because you want to be able to create links across different experiences so that you can relate them.
But you can also imagine that you might want to do that with a certain degree of caution.
You would not want to overgeneralize everything.
So there is a certain optimal degree of generalization,” she said.

As for psychiatric disorders where deficits are not as apparent, Heckers sees this study as being quite relevant.

He said that in psychiatric disorders you do not have a broken memory, but a system that has lost fidelity
and is not as accurate anymore.

In this regard it is relevant that those subjects who did generalize well had no idea that they were doing it
They appeared to have a memory that they had seen a given face and scene as a pair when in fact they had not.
If that is not a cognitive neuroscience model for hallucinations, then I don’t know what is,” said Heckers. References: Shohamy D, Wagner AD. Integrating memories in the human brain: hippocampal-midbrain encoding of overlapping events. Neuron 2008 October 23; 60:378-389. Kumaran D, Duzel E. The hippocampus and dopaminergic midbrain: old couple, new insights. Neuron 2008 October 23; 60: 197-200. Is this not a cognitive neuroscience model for hallucinations,

If generalization is to be explained by the alternative logical inference model
where memories are retrieved and analyzed on the spot
then it should correlate with activation of the brain areas involved in that process. However, Shohamy and Wagner found no link was found between hippocampal activation and performance in the generalization part of the tests.
That suggests that there is no additional retrieval process going on during generalization.
On the other hand, the researchers did find a correlation between generalization prowess
and hippocampal and midbrain activation during the learning phase. We found that all the action happened essentially while people were experiencing the individual events, what we call the premise event.
That is when people who later generalize well showed a lot of hippocampal activity.
People who later didn’t generalize well didn’t show this [ activity ] early on,” said Shohamy.

The results show that the brain events that predict the behavior
were happening not at the time of generalization
but earlier on, at the time of learning

M ental I llness C oncerns A ll

M ental I llness C oncerns A ll

Word comprehension engages the left ventrolateral prefrontal ( LVLPFC ) and posterior lateral-temporal cortices (PLTC). The contributions of these brain regions to comprehension remain controversial. We hypothesized that the PLTC activates meanings, whereas the LVLPFC resolves competition between representations. To test this hypothesis, we used functional magnetic resonance imaging (fMRI) to assess the independent effects of adaptation and competition on neural activity. Participants judged the relatedness of word pairs. Some consecutive pairs contained a common ambiguous word. The same or different meanings of this word were primed (e.g., SUMMER-FAN, CEILING-FAN; ADMIRER-FAN, CEILING-FAN). Based on the logic of fMRI adaptation, trials with more semantic overlap should produce more adaptation (less activation) in regions that activate meaning. In contrast, trials with more semantic ambiguity should produce more activation in regions that resolve competition. We observed a double dissociation between activity in the PLTC and lVLPFC. LPLTC activity depended on the amount of semantic overlap, irrespective of the amount of semantic ambiguity. In contrast, LVLPFC activity depended on the amount of semantic ambiguity. Moreover, across participants, the size of the competition effect - as measured by errors - was correlated with the size of the competition effect in the lVLPFC. We conclude that the LVLPFC is an executive mechanism within language processing. Thought disorder background material to work on ... work in progress - please help with feed back ... mica@jidgey.e7even.comThese reflections are what I carry in my thoughts, when I speculate about what is going on in the brain during active and continuing schizophrenia . Basically the brain is not 'functionally' all there when it should be. What is not there might come out of these studies of the brain in action, studies using the changes in oxygen and glucose within the brain cells when they are active or not, which are picked up by various scanning techniques, and try to show, where and when the cells in particular areas, are active and perhaps connected, when the brain is working in one way or another. Doing thinking or preparing for it. Stating my resting conclusion straightaway .... what starts out as a thought proceeding to some future conclusion, cannot hold on to the original imperium, guiding the direction in the face of the various adjustments that have to take place subsequently, to achieve the outcome, by managing the interchange with outside constraints, that arise on the way. It side tracks to unecessary associatiuons, or loses the momentum of the initial intention, and fails to come back to the intention.. where in the brain is an intention decided Because brains differ so much, the scientists need a good idea of what a person's brain activity looks like when they are thinking something to be able to spot it in a scan, but researchers are already devising ways of deducing what patterns are associated with different thoughts.· FAQ: Mind reading What have the scientists developed? They have devised a system that analyses brain activity to work out a person's intentions before they have acted on them. More advanced versions may be able to read complex thoughts and even pick them up before the person is conscious of them. How does it work? The computer learns unique patterns of brain activity or signatures that correspond to different thoughts. It then scans the brain to look for these signatures and predicts what the person is thinking. Researchers have shown they can read a person's intentions from the patterns of activity in the front of their brain. frontal 'Will' ? John-Dylan Haynes and colleagues said their findings could have important technical and clinical applications, “such as the further development of brain-computer interfaces, that might now be able to decode intentions that go beyond simple movements and extend to high-level cognitive processes”. Eight participants decided privately whether to add or subtract two numbers that appeared between 2.7 and 10.8 seconds after they had made their decision. Shortly after that, a response screen appeared, featuring the two possible answers, plus two other numbers, in randomly-arranged positions. The participants had to press a button corresponding to the number on the response screen that matched the act of subtraction or addition they had previously decided to make (thus revealing what their prior intention had been). The researchers were interested in the brain activity that occurred after the participants had formed their intention, but before the appearance of the two numbers that were to be added or subtracted. Crucially, because the answers and distractors were arranged randomly on the response screen, the participants could not start preparing the specific button press response they would need to make until the response screen appeared. This helped ensure relevant brain activity reflected the participants' chosen intention rather than motor preparation. The researchers found patterns of activity in several regions of the prefrontal cortex predicted whether the participants had chosen to add or subtract. In particular, decoding the spatial distribution of activity in the medial prefrontal cortex was able to predict the participants' intention with 70 per cent accuracy. There was no difference in overall levels of activity between the addition and subtraction decisions. An important question for future research is whether “the medial prefrontal cortex is generally involved in encoding specific tasks during intentional choices or whether encoding in this region is specific for tasks such as the preparation of addition and subtraction”, the researchers said. 'day dreaming ' the 'voices' 'prospective memory. Our findings suggest that the control process performed by the left prefrontal cortex directly reflects the demands of the environment on memory. Anatomy of Propective memorybr>1. Neuropsychologia. 2003 ;41(8):906-18 The role of the rostral frontal cortex (area 10) in prospective memory: a lateral versus medial dissociation. Burgess PW, Scott SK, Frith CD Institute of Cognitive Neuroscience, University College London (UCL), 17 Queen Square, London WC1N 3AR, UK. p.burgess@psychol.ucl.ac.uk Using the H(2)(15)O PET method, we investigated whether previous findings [ of regional cerebral blood flow (rCBF) changes in the polar and superior rostral aspects of the frontal lobes (principally Brodmann's area (BA) 10 ) during prospective memory (PM) paradigms ( i.e. those involving carrying out an intended action after a delay ] can be attributed merely to the greater difficulty of such tasks over the baseline conditions typically employed. Three different tasks were administered under four conditions:= baseline simple RT; attention-demanding ongoing task only; ongoing task plus a delayed intention (unpracticed); ongoing task plus delayed intention (practiced). Under prospective memory conditions, we found significant rCBF decreases in the superior medial aspects of the rostral prefrontal cortex (BA 10) relative to the baseline or ongoing task only conditions. However more lateral aspects of area 10 (plus the medio-dorsal thalamus) showed the opposite pattern, with rCBF increases in the prospective memory conditions relative to the other conditions. These patterns were broadly replicated over all three tasks. Since both the medial and lateral rostral regions showed: (a) instances where rCBF was lower during a more effortful condition (as estimated by increased RTs and error rates) than in a less effortful one; and (b) there was no correlation between rCBF and RT durations or number of errors in these regions, a simple task difficulty explanation of the rCBF changes in the rostral aspects of the frontal lobes during prospective memory tasks is rejected. Instead, the favoured explanation concentrates upon the particular processing demands made by these situations irrespective of the precise stimuli used or the exact nature of the intention. Moreover, the results suggest different roles for medial and lateral rostral prefrontal cortex, with the former involved in suppressing internally-generated thought, and the latter in maintaining it. Institute of Cognitive Neuroscience, University College London, 17 Queen Square, WC1N 3AR, London, UK. p.burgess@psychol.ucl.ac.uk Prospective memory (PM) refers to the functions that enables a person to carry out an intended act after a delay. Despite the ubiquity of this behaviour, little is known about the supporting brain structures and the roles that they play. In this study, eight healthy participants performed four different PM tasks, each under three conditions: a baseline, and two conditions involving an intention. In the first of the intention conditions, subjects were asked to make a novel response to a certain class of stimuli whilst [ at the same time ] performing an attention-demanding task. However, the expected stimuli never actually occurred. In the second intention condition subjects were expecting to see these stimuli as before, and they did occur on approximately 20% of trials. Relative to the baseline condition, increases in regional cerebral blood flow (rCBF) as estimated by oxygen-15 positron emission tomography technique across all four tasks were seen in the frontal pole (Brodmann's area 10) bilaterally, right lateral prefrontal and inferior parietal regions plus the precuneus when subjects were expecting a PM stimulus regardless of whether it actually occurred. Further activation was seen in the thalamus when the PM stimuli occurred and was acted upon, with a corresponding rCBF decrease in right lateral prefrontal cortex. It is argued that the first set of regions play a role in the maintenance of an intention, with the second set involved additionally in its realisation. more on prospective memory 'prospective memory experiment Cloze paragraph [ untoward words get in when they should not if the original guideline was sustained ] keeping to the point You should start by reflecting upon your own thinking in repose. Something starts it off – what, and how, is not understood ... a thought comes up ... is it random scanning or ? ...scanning for change, maybe an input from outside which leads to recall to programme; sometimes a kind of timer or calendar inside. waking us up to something we have to get on with …. Usually built on the routine structure for the day's 'events to come up' acquired from a routine that has been built up. We have, from what is going on outside, something that will recall us to the routine; sometimes there is something fresh which will then call up previous skills, habit , memories of the ways of tackling things, to find if they are relevant ; a system of ' connected thinking and doing' has been built up, and can be called upon, quite often not requiring much thinking, Sufferers may not have a built up routine that sustains and holds on to the internal preparation. what happens when the brain is just lying there just quiet, not thinking; the brain shows slow waves rippling and connecting areas in a seemingly a co-ordinated way It continues this way under sedation, and in early sleep and maybe early wake. Perhaps sorting out the transition between waking and sleeping What happens when we have nothing to do? Nothing to think about out there. That's to say there is nothing 'coming up' ... often called the' default ' position of the brain see day dreaming In this state the same bits of the brain become inactive, drop off, leaving the medium prefrontal to chatter away to the memory store in the hippocampus, the post cingulate region, and the lateral parietal area. The brain in this state is active using lots of glucose, out of all proportion to the oxygen usage. The medium prefrontal seems to be place of the WILL the executive which is vigilant and decides about what is good, bad, or indifferent, preventing interfering memories, selectively assessing relevance and usefulness. to be stored away or set aside in memory experience. Damage to this part of the brain leaves the person somewhat inert, and devoid of thought The study included 21 patients with schizophrenia and 22 healthy subjects. The group performed a straightforward task while undergoing functional magnetic resonance imaging in which they were asked to detect an infrequent target sound within a series of standard and novel sounds. In the healthy subjects, the default mode network resonated slowly and regularly as observed by blood flow. In the patients with schizophrenia, the activity in the brain increased and was significantly more irregular, although they performed equally well on the task. regions of the brain known previously to be individually abnormal in patients with schizophrenia, also function abnormally in concert in the default mode network. In addition, the extent of the default mode abnormalities correlated with the severity of auditory hallucinations, delusional thoughts, and attention deficits that are hallmarks of schizophrenia. Comparing the correlation coefficients of each pair of 116 brain regions between 15 patients and 15 controls. Then, the global distribution of the abnormal functional connectivities was examined. Experimental results indicated, in general, a decreased functional connectivity in schizophrenia during rest, and such abnormalities were widely distributed throughout the entire brain rather than restricted to a few specific brain regions. The results provide a quantitative support for the hypothesis that schizophrenia may arise from the disrupted functional integration of widespread brain areas. Although the exact role of the default network is unknown, it is thought to involve response to stimuli as well as self-referential and reflective activity that includes memory retrieval, inner speech, mental images, emotions, and planning of future events. Although in normal comparison subjects, the network [ parahippocampal, posterior cingulate and parietal, frontal ] , as measured by its blood flow with fMRI, resonates slowly and regularly; in schizophrenia the activity is increased and more irregular and also correlates with positive symptoms. they dispatched volunteer subjects around the Duke campus with cameras, instructing them to take pictures of campus scenes. The subjects were also instructed to remember the taking of each picture as an individual event, noting the physical conditions and their psychological state, such as their mood and associations with the subject of the images. Back in the laboratory, the subjects were shown a selection of campus photos they had not taken. Finally, they were shown a mix of their photos with those they had not taken while their brains were being scanned using functional magnetic resonance imaging (fMRI). They were asked to press a key to indicate whether they were seeing a photo they had taken, a photo seen in the laboratory or a new photo. In the widely used fMRI brain-scanning method, harmless magnetic fields and radio signals produce brain images that reveal blood flow to each part of the brain. Such blood flow reflects brain activity. "In autobiographical memory studies, it is very difficult to control the accuracy of memories and the various factors that affect encoding," said Cabeza. "This technique enabled us very good control of when and how the memories were formed and how they are recalled." The researchers found that recalling the autobiographical memories activated many of the same brain areas as laboratory memories -- the medial temporal lobe and the prefrontal cortex. "Thus, our study does support the basic validity and generalizability of laboratory memory studies," said Cabeza. However, in addition, autobiographical memory recall activated brain areas associated with "self-referential processing" -- that is, processing information about one's self. Autobiographical memories also activated brain regions associated with retrieval of visual and spatial information, and the memories more intensely activated the region associated with recollection. "Greater activation of self-referential areas makes sense because people are more involved in their own autobiographical memories," said Cabeza. "And greater activation of the visual and spatial areas fits well with evidence that we remember events that happen in the real world with more vivid sensory recall. Finally, greater activation of recollection areas in the hippocampus makes sense because memory of events involves more intense recollection." In the experiment, participants studied a total of 90 images in three categories -- celebrity faces, famous locations and common objects -- and then attempted to recall the images. Norman and his colleagues used Princeton's functional magnetic resonance imaging (fMRI) scanner to capture the participants' brain activity patterns as they studied the images. They then trained a computer program to distinguish between the patterns of brain activity associated with studying faces, locations or objects. The computer program was used to track participants' brain activity as they recalled the images to see how well it matched the patterns associated with the initial viewing of the images. The researchers found that patterns of brain activity for specific categories, such as faces, started to emerge approximately five seconds before subjects recalled items from that category -- suggesting that participants were bringing to mind the general properties of the images in order to cue for specific details. Patients with schizophrenia (N=21) and healthy comparison subjects (N=22) performed an auditory oddball task during functional magnetic resonance imaging (fMRI) Healthy comparison subjects and patients had significant spatial differences in the default mode network, most notably in the frontal, anterior cingulate, and parahippocampal gyri activity in patients in the medial frontal, temporal, and cingulate gyri correlated with severity of positive symptoms. Schizophrenia is associated with altered temporal frequency and spatial location of the default mode network. The authors hypothesized that this network may be under- or overmodulated by key regions, including the anterior and posterior cingulate cortex. In addition, the altered temporal fluctuations in patients may result from a change in the connectivity of these regions with other brain networks New Views of Aberrant Brain Processes in Schizophrenia Six articles in this issue use new brain imaging techniques to identify brain mechanisms that contribute to poor attention and auditory hallucinations in persons with schizophrenia. Functional magnetic resonance imaging (fMRI) enabled Gur et al. (p. 442) to demonstrate that patients’ difficulty in paying attention to visual stimuli is due to both insufficient activation of the brain systems needed for focusing and overactivation of areas that process distractors. Garrity et al. (p. 450) used a similar strategy with targets and distractors, but they used auditory stimuli and measured activation during the baseline auditory condition, the "default mode." Compared to healthy subjects, patients with schizophrenia had greater temporal fluctuations in this baseline or resting mode. Time-frequency analyses of EEG recordings by Ford et al. (p. 458) indicated that patients with auditory hallucinations were especially likely to have deficient phase synchrony of EEG oscillations before speaking. In healthy people, neural synchrony precedes self-generated speech and inhibits the person from responding to their own voice. High-density EEG applied by Ferrarelli et al. (p. 483) to patients with schizophrenia revealed deficits in sleep spindles, bursts of EEG activity generated by the thalamic reticular nucleus in conjunction with specific thalamic nuclei. Low sleep spindle activity therefore points to dysfunction in mechanisms involving these structures, which are involved in paying attention during waking. Leitman et al. (p. 474) related structural disturbances at the level of the primary auditory cortex to patients’ impaired ability to decode emotions according to voice tone modulation. Brain structure was examined by using diffusion tensor magnetic resonance imaging, which is sensitive to white matter abnormalities in schizophrenia. Diffusion tensor imaging also provided a means for Shergill et al. (p. 467) to examine whether the functional dysconnectivity in schizophrenia is due to disrupted anatomical connectivity. They found abnormalities in the white matter connections of the frontal cortex to the temporal and parietal cortexes and with the contralateral and temporal lobes. However, patients in whom the temporal lobe connections were relatively intact were more likely to have auditory hallucinations. Dr. Robert Freedman comments on these findings in an editorial on p. 385. Then we are likely to fall back on 'thought thoughts', left over from before, about something not a matter of present consideration, but a 'might be coming up ' yet undecided. We have left outside reality, but something is left open to keep an eye on it. One similar experience is of failing, after trying for a little time to do some of a crossword puzzle, Then leaving it to do something else quite different. To find on returning to the crossword the answers comes up quickly. Some work on the task left behind has been going on without awareness. Some brain function - the Will element - has kept on with the problem left behind; held somewhere for a solving connection to come up, 'knowing' - prepared - that the matter of the crossword will be returned to. Or. a choice is made that the thought to return to the crossword may be set aside, and the holding on to the answering mode, lapses. Or we may drift off into some prospecting thinking , a visualising, sometimes reality founded, Anticipating and trying out in 'imagination' what might come up ... a sort of testing ground, incorporating lessons from the past into plans for the future. Sometimes a 'let go into speculative inter - relationship in a different 'world' going on, with people speaking 'actors' - [ are these the voices heard by 3/4 people suffering from ongoing schizophrenia ] exchanging conversationally about some situation likely to come up but not yet settled. Sometimes a reflection on a back event , or a relationship, a rehearsal of something left over still to be done. Then perhaps a 'constructive day dream' [ how Ralph Richardson described 'acting' a part ] maybe a speculation about a possibility to come; An 'off piste' speculative thinking journey in a world, from which we can give ourselves a wake up nudge. All these require a 'holding on' to behaviour we expect to go back to, held ready to be resumed. It seems sufferers from schizophrenia may not get back to the point so efficiently, landing up somewhere else in thought They do not hold on in 'prospective memory. All the thinking depends upon selective attending to what matters, setting aside what is irrelevant for this moment, using only what is useful for the moment and the 'meanwhile' , plus what is there held in recent memory to bring into the picture on standby; and what has been stored away, available if needed, picking out what is needed but leaving out or setting on one side, connections not at the moment needed, but held in waiting, but that might come up later on. Long term patients in hospital might surprise by being seemingly indifferent to what ordinarily would bring up anxiety and help. Heart arrythmia addressed as 'bird wings': tooth abscesses apparently causing no pain, just ignored. What was going on was not attended to, in ordinary context Something is organising all this in the brain, picking out what is needed to think about later, setting aside other intrusive thought calling, getting other thought sequences into standby, setting others onward. But always holding on to a general purpose, picking it out of a lot of associations In schizophrenia holding on to this starting out purpose and it's context - the networks of stored away experience that might be relevant and contingent, does not always happen, thought and speech losing it's way, following unpurposeful associations, sometimes not being able to return to the original starting direction, and get back into line. Studies showed that, when patients experience auditory hallucinations (i.e. hear voices), activity is increased in Broca's area, that part of the brain which we normally use to generate conversation, or our own inner "mental" speech. This indicates that the words which people with schizophrenia hear as voices are self-generated in the same way that most of us would be saying the words of a poem or a prayer silently to ourselves. But why do those with schizophrenia not realise that they have generated the words themselves? Our researchers have shown that during hallucinations patients also activate their auditory cortex, the part of the brain which normally processes external speech. In short, when a patient is hearing voices, there is activity in two parts of the brain: in Broca's area, the part that would normally be involved in generating inner speech, and in the auditory cortex, the part that would normally be active while listening to another person speaking to them. Thus the person with schizophrenia produces words in their brain but then mistakenly activates the auditory cortex, and this tricks the brain into thinking that there must be some external source for the words. New knowledge of how the voices are generated opens up new ways of assessing the most appropriate treatment for each sufferer. For example, we can study the effect of a new treatment on the abnormal brain activity when a patient is ill. The visual hallucinations or delusions associated with psychosis are some say, also totally characteristic of the dream state, the function of which is to generate such hallucinatory realities. Neuroscientists have shown the same neuronal pathways are activated in psychotic episodes ???? Whilst dreaming we all believe completely in the reality of our dreams, just as the schizophrenic person believes in their reality. Psychiatry says 'keeping to the point' is all done by a process of WILL; an executive part of the brain [ probably dorso-lateral frontal lobe brain work ] which manages and decides, and paces forward planning, and carries it with the appropriate momentum on a particular course, holding it on to the final goal, , setting aside unnecessary or unrequired associations which might come up, step in, but that the WILL decides are not to interfere at any particular time along the way. Often without a feeling of conscious effort. In schizophrenia the WILL is enfeebled and not fully in charge, and is not always awoken up to take command, to make a response that is in a properly assessed and examined context; so that odd thoughts , misplaced thoughts, butt in, or required ones don't start, or don't turn up or turn up innappropriately. The Will is not 'tuned in' and does not recognise the faults which then go uncorrected or become erroneously fitted in to interfering exchanges with the outside; maybe conversations, or work in progress, so that the sense of what is required does not happen. Prompting, waiting, cueing in, 'jigging reminders', may keep a direction, a conversation, a task, going on. Leading questions may be answered briefly and relevantly- there is lead structure to draw in appropriate response - but questions which leave an answer 'hanging in the air' may find perplexing responses. link to Home Page   link to Schizophrenia E-mail reaction is welcome mica@jidgey.e7even.com