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 brain activation differences as deficits in the steps of thinking in schizophrenia.
Several are summarised below.

This is an example - a summary of a latest King's College study

Structural magnetic resonance imaging (MRI) studies
suggest that the at-risk mental state is associated with reduced grey matter volume in regions that are also abnormal in schizophrenia,
and a recent functional MRI study reported differential prefrontal activation in individuals with an at-risk mental state
relative to controls and patients with schizophrenia during a visual oddball paradigm.

Cognitive tasks

N-back memory task

In all conditions participants were presented with a series of letters which they viewed using a prismatic mirror.
The interstimulus interval was 2 s.
During the baseline (0-back) condition, individuals were required to move a joystick to the left when the letter ‘X’ appeared.
During the 1-back and 2-back conditions, participants were required to press a button on the joystick with their right index finger if the currently presented letter
was the same as that presented one or two letters beforehand respectively.
The three conditions were presented in 10 alternating 30 s blocks matched for the number of target letters per block (i.e. two or three), in pseudorandom order.
Reaction time and the accuracy of the responses were recorded electronically by computer.

Overt verbal fluency task

Participants were required to say aloud a word beginning with a visually presented letter.
The stimuli, each subtending an angle of 5°, were presented visually on a black screen, viewed through a mirror.
Cognitive load was modulated with two levels of task difficulty, ‘easy’ and ‘hard’ conditions,
which involved letters that differed with respect to the ease with which volunteers can usually generate words beginning with them.

The ‘easy’ condition involved the letters L, T, C, P, S; the ‘hard’ condition: O, N, E, F, G.14
Incorrect responses were defined as words that were proper names, repetitions or grammatical variations of the previous word,
and ‘pass’ responses. Letters were presented in 28 s blocks of seven stimuli at 4 s intervals.
The control condition of word repetition comprised 28 s blocks of 7 presentations of the word ‘rest’ at 4 s intervals,
which participants were required to read aloud. Five blocks of each condition (hard/easy/repetition) were presented in random order.

Verbal responses were recorded via an MRI-compatible microphone on Cool Edit 2000 for Windows.
To ensure that participants heard their responses clearly, their speech was transmitted by an MRI-compatible microphone,
amplified by a computer sound card and relayed back through an acoustic MRI sound system (Ward Ray, Hampton Court, UK),
and noise-insulated, stereo headphones at a volume of 91 plus or minus 2 dB.

The differential activation was not attributable to impairments in task performance,
as there were no significant differences in the speed or accuracy of responses across groups,
and the analysis selectively modelled the BOLD response to those trials associated with correct responses.
The lack of difference in behavioural performance allows the interpretation of activations to proceed
knowing that the psychological task is being carried out to an equal level by all participants
and hence, any remaining difference in activation is likely to be due to the disorder of interest, rather than a non-specific correlate of poor performance.

It is difficult to get what this study means by 'less activation' in terms of what is actually happening 'real time' .....
they suggest ' lack of interest' ; that does not stand up if the behaviour results were just as good in all groups: psychosis, 'impending', controls

Persons with schizophrenia often cannot automatically discriminate important from unimportant information.

Gur et al. 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.

1.

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 presenting the distractor stimuli over-activated 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.

2.

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

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. 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 that 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.

3.

Ferrarelli et al. 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.

4.

Inhibition is also the theme of the demonstration by Ford et al. 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 to distinguish their own speech from others.

Ford et al. hypothesize that malfunction of this system,
demonstrated as failure of pre-speech synchronization and the lack of inhibition of N1,
results in failure of the persons with schizophrenia
to distinguish their speech from that of others.

[ N.B in trying to find an answer to a crssword clue - I sometimes try to find the answer by running silently, the first letter in going through the alphabet downwards - the internal instruction. On this occasion I had got to M saying it internally, when the answer to the crossword came immediately - it was P. as though the instruction had carried on ahead of my hearing and speaking to myself - something the same ? ]

5.

Shergill et al. 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.

6.

Leitman et al. also used 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:
(a)the failure to inhibit activation by distractors in the study by Gur et al.,
(b)the failure to maintain stable default processing in the study by Garrity et al.,
and(c) 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.

Two fMRI studies used 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.

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.

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 a figure that A is greater than B,
and that B is 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

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.

Inhibition 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).

Footnotes Greater hippocampal-midbrain engagement during integrative encoding [ that is ... relevant associating done at the time of the event ]
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. 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 analysed 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 behaviour 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.

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.

Heckers also studies learning and memory in humans and previously showed that generalization is related to activation of the hippocampus The relationship between the hippocampus and the ventral tegmental area is not entirely novel, but what they have shown is that generisation takes place at the time of encoding. That is novel, and this might be the first study that supports the Lisman and Grace model ... [ the hippocampus and the midbrain dopaminergic neurons of the ventral tegmental area (VTA) form a functional loop.
Activation of the loop begins when the hippocampus detects newly arrived information that is not already stored in its long-term memory.
The resulting novelty signal is conveyed through the subiculum, accumbens, and ventral pallidum to the VTA where it contributes
(along with salience and goal information) to the novelty-dependent firing of these cells.
In the upward arm of the loop, dopamine (DA) is released within the hippocampus; this produces an enhancement of LTP and learning.
These findings support a model whereby the hippocampal-VTA loop regulates the entry of information into long-term memory.] 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. In this study Shohamy found no correlation between generalizability and the striatum. Also, in collaboration with colleagues at Rutgers, Shohamy previously reported that while Parkinsomism patients have trouble learning episodes,
once they do, they have no trouble generalizing (see Shohamy et al., 2006

. 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 over-generalize 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 any more. In this regard it is relevant that for those subjects who did generalise well
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 [ hippocampal 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 at the time of learning earlier on, 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 or 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 ...

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. 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.

John-Dylan Haynes and colleagues 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 – distractors - , 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 that 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.

Our findings suggest that the control process performed by the left prefrontal cortex
directly reflects the demands of the environment on memory.

Anatomy of Prospective memory

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.

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 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:-
1. baseline simple RT;
2. attention-demanding ongoing task only;
3. ongoing task plus a delayed intention (unpracticed);
4. 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 condition.
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.

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 ] expecting to perform 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 were seen in regional cerebral blood flow (rCBF)
as estimated by oxygen-15 positron emission tomography technique
across all four tasks

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 decrease in right lateral prefrontal cortex.

It is argued that the first set of regions play a role in the maintenance of an intention,
the second more on prospective memory

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' generalisation has been built up, and can be called upon,
quite often not requiring much thinking.

Sufferers may not have a built up the routine that sustains and holds on to the internal preparation.

What happens when the brain is just lying there just quiet, not thinking
is that 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

A 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.[ generalisation ]

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 an 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 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?

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 [ the prefrontal director - the chief executive ] 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.

More theoretical background

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 [ what had been before as ] the default mode network.
Nodes of this default network play a role in the neurobiology of schizophrenia; the method
is useful 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.
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.

more on brain networking linkages

It has been proposed that fast oscillations (?, ?) may synchronize neurons within local circuits, while slower oscillations (?, ?, ?) may coordinate the synchronization of neurons across brain regions, and also gate high-frequency oscillations (e.g., Sirota et al., 2008

[ Ed:- that is the small world brain networks above may be linked up withon themselves by synchronising oscilation rates. .. I'll move the tecnical quotes as an addendum when I get the anchoring right !!] ]

Methods

To analyze oscillatory synchronization, it is necessary to decompose the EEG in the frequency domain.
Simple methods are filtering and frequency analysis within a fixed epoch, but these are limited in time and frequency resolution.
Better methods perform a joint time/frequency analysis, such as with wavelets or a windowed Fast Fourier Transform (FFT).
There are also methods to analyze oscillatory synchrony between brain regions,
which typically involve the application of wavelets or windowed FFTs to obtain power or phase coherence between the signals measured at separate sensors.
(For review, see Roach and Mathalon, 2008).

Two basic types of oscillations have been defined:
1) evoked oscillations, which are phase-locked to a stimulus (or other reference time point);
and 2) induced oscillations, which are not strongly phase-locked to the stimulus, but are jittered in latency across trials.

The measures of oscillations that are commonly used complement these definitions:
evoked power measures the power of oscillations that are phase-locked to the stimulus,
and are computed from the average of single trials (the average ERP).
Total power includes both evoked and induced oscillations, and is measured in the average of single-trial power spectra.
The phase-locking factor (or value) measures the degree to which an oscillation is phase-locked to a stimulus, and is independent of power.

Oscillation Abnormalities in Schizophrenia A variety of abnormalities of fast oscillations have been observed in schizophrenia. A partial list includes the following:

* Auditory steady-state response (ASSR).
o Reduced power, phase-locking in ? range.
o Found in chronic (Brenner et al., 2003; Hong et al., 2004; Kwon et al., 1999; Light et al., 2006; Teale et al., 2008),
first episode (Spencer et al., 2008b), early-onset schizophrenia (Wilson et al., 2007); unaffected siblings of schizophrenia (Hong et al., 2004);
also bipolar disorder (O'Donnell et al., 2006). ,p. * Early visual-evoked ?.
o Reduced phase-locking (Spencer et al., 2008a).
* Early auditory-evoked ?.
o Reduced in 2/3 studies (deficit with increasing task demand?) (Gallinat et al., 2004; Roach and Mathalon, 2008; Spencer et al., 2008a). * Motor-related ?.
o Reduced phase-locking (Ford et al., 2008).
* Inter-regional synchronization in perception.
o Reduced phase coherence (Uhlhaas et al., 2006).
* Perception-related ? (Spencer et al., 2004).
o Frequency reduced to ?.
o Phase-locking positively correlated with positive symptoms.

* Working memory.
o Reduced power (Basar-Eroglu et al., 2007; Cho et al., 2006).

In lower frequency bands, oscillation abnormalities include the following:

* Visual steady-state response.
o Increased power at low stimulation frequencies (? and lower), but decreased power at ? and ? (e.g., Jin et al., 1997; Krishnan et al., 2005).
o Prolonged onset and offset of the visual SSR to ? frequency stimulation (Clementz et al., 2004).
* Increased "noise" or induced ? and ? during rest (Boutros et al., 2008) and task performance (Winterer and Weinberger, 2004).

* Sleep spindles (~12-15 Hz) (Ferrarelli et al., 2007).
o Generated by thalamocortical interactions.
o Decreased incidence and power.

If we can draw any conclusions at this point in time, it might be that high-frequency oscillations are generally reduced in power/phase-locking,
while low-frequency oscillations may be increased, and that inter-regional synchronization is impaired.

Mechanisms underlying ? oscillation abnormalities

The mechanisms underlying ? oscillations are perhaps the best understood out of all the oscillations,
and the convergence between this research and postmortem studies of neural circuitry abnormalities in schizophrenia
has spurred much of the interest in ? oscillations as potential biomarkers.
Below is a summary of some of the most salient findings in this area: Inhibitory interneurons.

* Fast-spiking, perisomatic-targeting, parvalbumin (PV)-expressing interneurons (chandelier and basket cells).
o May phase the output of pyramidal cells and other interneurons, thought to be critical for ? rhythm generation (Whittington and Traub, 2003).
o In schizophrenia show reduced GABA synthesis, PV expression (Gonzalez-Burgos and Lewis, 2008).

Reduced synaptic connectivity.

* Neuronal density appears to be increased in schizophrenia, but cortical volume is decreased.
Thus, the interneuronal space containing dendrites and axons (neuropil) is reduced. May reflect reduced synaptic connectivity (Selemon and Goldman-Rakic, 1999).

* Supported by decreases in:
o Spine density, somal size, and dendritic fields of pyramidal cells.
o Presynaptic markers.
* Consistent with MRI evidence of cortical thinning, volume reduction.

NMDA receptor hypofunction

* Possible unifying model (e.g., Javitt and Zukin, 1991).

* NMDAr antagonism (e.g., PCP, ketamine) produces:
o Schizophrenia-like symptoms in healthy individuals, exacerbation of symptoms in patients (Krystal et al., 2003).
o Increased cortical excitability (Homayoun and Moghaddam, 2007) and ? power (Pinault, 2008; Roopun et al., 2008), possibly via decreased excitation of PV interneurons.
o Decreased expression of PV, GAD67 (GABA synthesis) (Kinney et al., 2006).
o Decreased synaptic connectivity (Hajszan et al., 2006).

References: Basar-Eroglu C, Brand A, Hildebrandt H, Karolina Kedzior K, Mathes B, Schmiedt C (2007). Working memory related ? oscillations in schizophrenia patients. Intl J Psychophysiol 64:39-45. Abstract
Boutros NN, Arfken C, Galderisi S, Warrick J, Pratt G, Iacono W (2008). The status of spectral EEG abnormality as a diagnostic test for schizophrenia. Schizophr Res 99:225-237. Abstract
Brenner CA, Sporns O, Lysaker PH, O'Donnell BF (2003). EEG synchronization to modulated auditory tones in schizophrenia, schizoaffective disorder, and schizotypal personality disorder. Am J Psychiatry 160:2238-2240. Abstract
Cho RY, Konecky RO, Carter CS (2006). Impairments in frontal cortical {?} synchrony and cognitive control in schizophrenia. Proc Natl Acad Sci USA 103:19878-19883. Abstract
Clementz BA, Keil A, Kissler J (2004). Aberrant brain dynamics in schizophrenia: delayed buildup and prolonged decay of the visual steady-state response. Cogn Brain Res 18:121-129. Abstract
Ferrarelli F, Huber R, Peterson MJ, Massimini M, Murphy M, Riedner BA, Watson A, Bria P, Tononi G (2007). Reduced sleep spindle activity in schizophrenia patients. Am J Psychiatry 2007 164:483-492. Abstract
Ford JM, Roach BJ, Faustman WO, Mathalon DH (2008). Out-of-synch and out-of-sorts: dysfunction of motor-sensory communication in schizophrenia. Biol Psychiatry 63:736-743. Abstract
Gallinat J, Winterer G, Herrmann CS, Senkowski D (2004). Reduced oscillatory ?-band responses in unmedicated schizophrenic patients indicate impaired frontal network processing. Clin Neurophysiol 115:1863-1874. Abstract
Gonzalez-Burgos G, Lewis DA (2008). GABA neurons and the mechanisms of network oscillations: implications for understanding cortical dysfunction in schizophrenia. Schizophr Bull 34:944-961. Abstract Hajszan T, Leranth C, Roth RH (2006). Subchronic phencyclidine treatment decreases the number of dendritic spine synapses in the rat prefrontal cortex. Biol Psychiatry 60:639-644. Abstract
Homayoun H, Moghaddam B (2007). NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J Neurosci 27:11496-11500. Abstract
Hong LE, Summerfelt A, McMahon R, Adami H, Francis G, Elliott A, Buchanan RW, Thaker GK (2004). Evoked ? band synchronization and the liability for schizophrenia. Schizophr Res 70:293-302. Abstract
Javitt DC, Zukin SR (1991). Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 148:1301-1308. Abstract
Jin Y, Potkin SG, Sandman CA, Bunney Jr WE (1997). Electroencephalographic photic driving in patients with schizophrenia and depression. Biol Psychiatry 41:496-499. Abstract
Kinney JW, Davis CN, Tabarean I, Conti B, Bartfai T, Behrens MM (2006). A specific role for NR2A-containing NMDA receptors in the maintenance of parvalbumin and GAD67 immunoreactivity in cultured interneurons. J Neurosci 26:1604-1615. Abstract
Krishnan GP, Vohs JL, Hetrick WP, Carroll CA, Shekhar A, Bockbrader MA, O'Donnell BF (2005). Steady state visual evoked potential abnormalities in schizophrenia. Clin Neurophysiol 116:614-624. Abstract
Krystal JH, D'Souza C, Mathalon D, Perry E, Belger A, Hoffman R (2003). NMDA receptor antagonist effects, cortical glutamatergic function, and schizophrenia: toward a paradigm shift in medication development. Psychopharmacol 169:215-233. Abstract
Kwon JS, O'Donnell BF, Wallenstein GV, Greene RW, Hirayasu Y, Nestor PG, Hasselmo ME, Potts GF, Shenton ME, McCarley RW (1999). ? frequency-range abnormalities to auditory stimulation in schizophrenia. Arch Gen Psychiatry 56:1001-1005. Abstract
Light GA, Hsu JL, Hsieh MH, Meyer-Gomes K, Sprock J, Swerdlow NR, Braff DL (2006). ? band EEG oscillations reveal neural network cortical coherence dysfunction in schizophrenia patients. Biol Psychiatry 60:1231-1240. Abstract
Pinault D (2008). N-methyl d-aspartate receptor antagonists ketamine and MK-801 induce wake-related aberrant {?} oscillations in the rat neocortex. Biol Psychiatry 63:730-735. Abstract
Roach BJ, Mathalon DH (2008). Event-related EEG time-frequency analysis: an overview of measures and an analysis of early ? band phase locking in schizophrenia. Schizophr Bull 34:907-926. Abstract
Roopun AK, Cunningham MO, Racca C, Alter K, Traub RD, Miles A. Whittington MA (2008). Region-specific changes in ? and ?2 rhythms in NMDA receptor dysfunction models of schizophrenia. Schizophr Bull 34:962-973. Abstract
Selemon LD, Goldman-Rakic PS. The reduced neuropil hypothesis: a circuit based model of schizophrenia. Biol Psychiatry. 1999 Jan 1;45(1):17-25. Review. Abstract
Singer W (1999). Neuronal synchrony: a versatile code for the definition of relations? Neuron 24:49-65, 111-125. Abstract
Sirota A, Montgomery S, Fujisawa S, Isomura Y, Zugaro M, Buzsáki G (2008). Entrainment of neocortical neurons and ? oscillations by the hippocampal ? rhythm. Neuron 60:683-697. Abstract
Spencer KM, Nestor PG, Perlmutter R, Niznikiewicz MA, Klump MC, Frumin M, Shenton ME, McCarley RW (2004). Neural synchrony indexes disordered perception and cognition in schizophrenia. Proc Natl Acad Sci USA 101:17288-17293. Abstract
Spencer KM, Niznikiewicz MA, Shenton ME, McCarley RW (2008a). Sensory-evoked ? oscillations in chronic schizophrenia. Biol Psychiatry 63:744-747. Abstract
Spencer KM, Salisbury DF, Shenton ME, McCarley RW (2008b). ?-band auditory steady-state responses are impaired in first episode psychosis. Biol Psychiatry 64:369-375. Abstract
Teale P, Collins D, Maharajh K, Rojas DC, Kronberg E, Reite M (2008). Cortical source estimates of ? band amplitude and phase are different in schizophrenia. NeuroImage 42:1481-1489. Abstract
Uhlhaas PJ, Linden DEJ, Singer W, Haenschel C, Lindner M, Maurer K, Rodriguez E (2006). Dysfunctional long-range coordination of neural activity during Gestalt perception in schizophrenia. J Neurosci 26:8168-8175. Abstract
Wilson TW, Hernandez O, Asherin RM, Teale PD, Reite ML, Rojas DC (2008). Cortical ? generators suggest abnormal auditory circuitry in early-onset psychosis. Cereb Cortex 18:371-378. Abstract
Whittington MA, Traub RD (2003). Interneuron diversity series: inhibitory interneurons and network oscillations in vitro. Trends Neurosci 26:676-682. Abstract
Winterer G, Weinberger DR (2004). Genes, dopamine and cortical signal-to-noise ratio in schizophrenia. Trends Neurosci 27:683-690. Abstract

Daydreaming

Robert Freeman [ Ed. Am Journal of Psychiatry ] comments on six studies of brain connecting in schizophrenia

A significantly larger number of protein spots were differentially expressed in the anterior (n = 43) compared to the posterior (n = 16) hippocampus, representing 34 and 14 unique proteins, respectively. These proteins are involved in cytoskeleton structure and function, neurotransmission and mitochondrial function. CONCLUSION: Based on the aberrant protein expression profiles, the anterior hippocampus appears to be more involved in schizophrenia pathogenesis than the posterior hippocampus. Furthermore, consistent with previous findings, we found molecular evidence to support abnormal neuronal cytoarchitecture and function, neurotransmission and mitochondrial function in the schizophrenia hippocampus.