Page 2

Background Studies

Links to Background studies with online reference to the documents The first four are directly relevant - more recent studies, they indicate in particular, what it is in the management of memory, working in living situations that makes that living harder for sufferers with continuing schizophrenia, studies confirming the difficulties that would arrive from any reduced Working Memory Capacity, thereby giving credence to the 2. REIF study ; the others are significant in providing a background :- 1. - ... 2a. .,..2. b- ... 3. - ,..4. - ... 5. - ... 6. - ... 7. - ...8. - ...9. - ...10. The old belief that the brain was as it was and would stay that way has given way to the surprise of continuing new brain cell creation in an area around the lateral ventricles, and the hippocampal area. Those in the hippocampal area play a crucial part in managing the working required from memory - that is the inner updating that has to be done from what is happening now, that needs to be attended to, as we move forward in life - current life matters, and prospective possibilities. But, in schizophrenia the hippocampus ability to new cell creation is reduced [ 2. 1. A correspondence is found between the level of hippocampal neurogenesis cells and the level of effective working memory,. Siebzehnrubl et al [ Epilepsia 49 (suppl 5) 55-65 2008 ] a postdoctoral researcher in neuroscience in the UF College of Medicine a need unmet, The researchers studied how stem cells in a memory-related region of the brain, called the hippocampus, proliferate and change into different types of nerve cells. Scientists have been unsure of the significance of that process in humans. Over the past two decades, several studies have shown that new nerve cells are generated in the hippocampus. In animal studies, disrupting nerve cell generation resulted in the loss of memory function, whilst increasing the production of new nerve cells led to improved memory. To investigate whether the same is true in humans, the UF researchers, in collaboration with colleagues in Germany, studied 23 patients who had epilepsy and varying degrees of associated memory loss. They analyzed stem cells from brain tissue removed during epilepsy surgery, and evaluated the patients' pre-surgery memory function. In patients with low memory test scores, stem cells could not generate new nerve cells in laboratory cultures, but in patients with normal memory scores, stem cells were able to proliferate. That showed, for the first time, a clear correlation between patient's memory and the ability of their stem cells to generate new nerve cells. "The findings suggest that if we can increase the regeneration of nerve cells in the hippocampus we can alleviate or prevent memory loss in humans," back to top 2a. This study points to hippocampal change preceding and bringing on schizophrenia [ Schobel et al:- In the September Archives of General Psychiatry, 2009 ] was on 18 'prodroma subjects who met clinical criteria for being at ultra high risk of developing psychosis. These subjects presented symptoms that did not quite rise to the level seen in psychosis. For example, prodromal subjects might profess unusual ideas that seem less compelling than delusions. During the two years of follow-up, seven of the prodromal subjects became psychotic. Of the three dysfunctional areas seen in subjects with more established disease, only the CA1 subfield in the hippocampus appeared awry in these subjects. Notably, high activity in this area predicted the eventual emergence of psychosis. In fact, it did so with a positive predictive value of 71 percent and a negative predictive value of 82 percent. Now confirmation from a multi site study . Archives General Psychiatry 2011 May;68(5):489-95. ... Mechelli at al. Neuroanatomical abnormalities that predate the onset of psychosis: a multicenter study. Individuals at high risk for psychosis [ schizophrenia ] show alterations in regional gray matter volume regardless of whether they subsequently develop the disorder. In the Ultra High Risk population, reduced left parahippocampal volume was specifically associated with the later onset of psychosis. Alterations in this region may, thus, be crucial to the expression of illness. Back to Rehabilitation back to top 2. Reif et al 2006 ... the penultimate two paragraphs in Discussion ... quote This study is on post-mortem material held ' in stock ' much earlier. The hippocampal area in tissue from schizophrenia is compared with that from mood disordered people and normal controls. " Does the finding of decreased Adult Neurogenesis [ AN ] in Schizophrenia make sense? Sz is known to go along with several cognitive deficits, which is stable over time, that is, trait rather than state dependent. The prime role of hippocampus is rather memory formation than affect regulation. Thus, diminished Adult neurogenesis, which has been suggested to result in impaired memory formation, will contribute to the cognitive impairment seen in Sz; improvement of cognitive functioning in Sz by clozapine might be due to the increase of AN seen in animal studies. As learning, exercise, and enriched environment all increase AN as well, this directly points toward non-pharmacological treatment of schizophrenics. The preliminary finding of reduced AN in Sz provided in the present study is thus worth being pursued further." In post-mortem examination of the hippocampal area in schizophrenia [ - a surprise finding as the authors were looking for change in affective llnesses - ] the area now known to continue producing new cells, neurogenesis was depleted. Depleted hippocampal neurogenesis means reduced working memory capacity. Without enough working memory capacity [ 3.] people with schizophrenia are limited in what they can proceed with on their own - they go astray, they give up often in a mess. They need help in starting, and maintaining, success in getting regularly into activities of interest during the week, a routine that will stabilise the illness; routine that is a normal support foir working people and domestic management. How is it this research finding by Reif et al - accidental, as it was not the initiating hypothesis - has not been seized upon, confirmed by others, and lauded in the schizophrenia field of interest There aren't many hard facts in schizophrenia and this needs to be confirmed, to be given prominence . The trouble is partly that research has to wait for Grants. Grants are obtained by eminences. They have their own hobby horses - eminences don't follow- they lead !!! Even in the wrong direction with their slaves !!!! This research is not sufficiently bang up to date for a newsworthy puff. The finding was not - a success - the one looked for. It was serendipitous, often the changing discovery. But it is a crucial discovery. Perhaps overlooked because it was not possible at that time to link it to working memory capacity back to Rehabilitation back to top now Gold has done that. Gold paper Sufferers from persistent steadied schizophrenia on standard medication were asked to recognise and place colour worded items, declaring them at one second and four seconds after exposure What was examined was the number of items :- 1. accurately stored 2. retained to be able to show them at 4 secs. Schizophrenia subjects were as accurate as controls, but, they did not hold on to the items at 4 secs. The situation at delay showed no deterioration of capacity nor of precision. They held what was stored. They did not store at first point. The problem is in the use of the initial storage capacity. They recognise the placement and the number at 1 second . They fail to show them at 4secs. The failure is in the capacity to accept, so that they cannot keep them where they could be drawn on later. ' Visual WM representations are neither less precise nor more prone to decay in schizophrenia. Instead, patients exhibit a reduction in the number of items they can concurrently maintain in WM '. Schizophrenia fails on working memory capacity. The ability to carry incoming information, to store what will be relevant later on is crucial to the completion of the sequences in behaviour that enable ordinary living tasks to be carried on . back to top 3. link to the Gold et al paper ... quote ... " Patients show clear reductions in the number of items that can be stored in WM [ Ed Working Memory ] but no evidence that their WM representations are less precise or less stable than those of healthy individuals " ... demonstrate that in residual schizophrenia there is not enough working memory capacity - they cannot hold on to enough matters on hand relevant to what is going on to keep up and cope with life's difficulties, unless they are limited in scope. There is not enough available working memory to address, hold on to, update and accomodate all the background relevance that are necessary towards achieving a successful conclusion for an intention. The brain connections needed, are not assembled, are not there when wanted. If it is so reduced, you stumble along the way of what you wanted to do and achieve, often the intention cannot get there: there is just not enough background memory held onto, to keep a focus, to keep out irrelevant distractions. This recent study finds, importantly, limited working memory capacity, in residual schizophrenia. For those left with delivering after-care to people with residual schizophrenia, this requires clinical recognition. There is not enough working memory to rehabiltate themselves. They fall behind With working memory so reduced you cannot rehabilitate yourself. Working memory is what you call upon to keep up with what comes along when carrying forward a decision to do something. Help into a routine becomes a clinical need. [ for those whose illness arrives later than adolescence, there is often already a settled routine to fall back on even if it does not update. There is a banked memory of personal skills, domestic experience, some social network. The future for social survival is better. Active intervention in schizophrenia for those without a workable routine, is not a social need. It's a medical imperative. They need somehow to establish themselves in a daily and weekly routine, that they can look forward to, that holds their attention and gives a lead to engagement. back to top The next three studies explain the disability, They also point to how to deal with it. The remaining studies paint in the background. 4. Another study [ this link ...used to work ... Raalten... but if not, link to a bigger journalist summary ] points to a remedy. " When encouraged and accompanied, given the opportunity to practice, sufferers do store what they have memorised: equally as well as for 'control subjects', by 'chunking'. So, that is, a routine can be learnt This study now confirmed :- Koch et al Koch et al "... First evidence from studies with schizophrenia patients indicates that the potential to profit from short-term practice under stable learning conditions (ie, when the same stimulus material is repeatedly being processed)s is largely preserved. van Raalten and colleagues found that, although the patients' learning ability was impaired when frequent information updating was required, their capability to profit from practice under stable learning conditions was unimpaired. Here, patients showed significant performance improvements and significantly reduced WM activity with increasingly successful processing. back to top cp Elvevaag et al - across rehearsing a simple game schizophrenia sufferers do as well as normal controls. but not with an additional prospective instruction.by repetition automation – chunking – can be done in schizophrenia as normal, requiring less and less working memory with practice. So routines when met with repeatedly, are stored away. There is then an internal framework which points towards outside activities, getting to them already practised, so sparing working memory that would not be able to make the access de novo. The making of these routines by themselves is beyond their reduced working capacity. . Sufferers cannot readily rehabilitate by themselves But routines, helped into by mentors , entering into them made easy until established , then practiced does give sufferers an internal mapping long-term memory store, leading to engagement in the programme of activity within a week, that they then can keep up with. It has been rehearsed, and the working memory capacity, even reduced, allows for this engagement in something that is now not new, but ' chunked' and familiar. Sufferers need a help over the first steps that they cannot achieve themselves. After that they can do it themselves. back to top back to top of Rehabilitation page . 6. Working memory is the mental ability to hold small amounts of information in an active, readily available state for a short period of time, typically a few seconds. Conversely, long-term memory involves storing a potentially unlimited amount of information for an indefinite period of time. Squire and colleagues examined four memory-impaired patients with damage to their medial temporal lobes (MTL), a region of the cerebral cortex containing the hippocampus and linked to long-term memory formation. The four patients were asked to briefly study an arrangement of objects on a table, then reproduce the objects' relative positions on another table. When the number of objects was three or less, the patients' ability to recall was similar to that of control subjects without brain damage. The impaired patients easily remembered where the objects had been placed in relation to each other. But "their performance abruptly collapsed when the limit of working memory was reached," said Squire. The patients could not remember the locations of four or more objects because doing so involved tapping into long-term memory functions in the medial temporal lobe. 5. Mazhari et al :- 2010 Oct 30;179(3):253-8. Epub 2010 May 21. Abstract Spatial working memory (SWM) dysfunction is a central finding in schizophrenia; however, more evidence of impaired maintenance over time is required. Consequently, the present study examined SWM maintenance over short unfilled delays, and with encoding equated. The influence of a vertical reference frame to support maintenance was also investigated. The performance of 58 patients with schizophrenia and 50 healthy controls was assessed using the Visuo-Spatial Working Memory (VSWM) Test across three unfilled delays (0, 2, and 4s). Inaccuracy of direction and distance responses was examined at each delay duration. The results showed that performance was significantly less accurate for both distance and direction responses at 2 and 4s delays in schizophrenia, but was not significantly different from controls at the 0s delay. Patients showed a particularly marked loss of accuracy between the time interval of 0-2s. Furthermore, schizophrenia participants exhibited significantly greater response variability at the vertical axis of symmetry than controls at the 2 and 4s delays, but not at the 0s delay. These data clearly show both impaired maintenance over time and difficulty using a vertical frame of reference in schizophrenia. The latter findings may reflect, in part, dysfunctional reference-related inhibition[ ??? ed ]

10. 20. 40. 50. 90. 100. 80 120. 110. 130. 140. 140. 150. 180. 170. 250. 240. 260. 270. 280 290 300 310< BR> 250 320

Is this what happens - early damage followed by a releaser causing further damage in late adolescence and after ? Teng KY et al Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA. Animals with a neonatal ventral hippocampal lesion (NVHL) develop abnormal behaviors during or after adolescence, suggesting that early insults can have delayed consequences. . . .These are alive cells taken in surgery used to see if they were there in the hippocampus. The result where there is neurogenesis found in the tissue , memory capacity is alive. When neurogenesis was absent - that was where there was no recent memory neurogenesis in the hippocampus is needed for a working memory Is this when the loss of neurogenesis occurs ? The hippocampal CA1 sub-field becomes overactive in schizophrenia and that this dysfunction foretells which high-risk subjects will develop psychosisThe findings suggest that, in schizophrenia, oxygen use increases in the hippocampal CA1 subfield and the orbitofrontal cortex. In contrast, it seems to decrease in the dorsolateral prefrontal cortex. An old false record- ? a delusional system cannot be reclaimed , held aside, and eliminated, so that it is possible to move on? Recognise that when the illness strikes the person with schizophrenia is left to cope with whatever level of personal, domestic, work , and experience in relationships that they possessed at the time the illness struck. They do not easily move on from their own efforts. Without enough working memory the whole system of calling upon memory is interrupted. Seeing and realising a prospect beyond a simple short term will be too difficult, except sometimes where there is already a preserved body of practical knowledge and interest in a particular area before the illness struck. They can connect to a programme of activities in the day and week once they have been helped into it, in increments -'chunking'. But something remains unexplained that this study leaves for further understanding. Although working memory is freed up by 'chunking' enough to establish, hold, and engage, in a routine already established by 'chunking' - the freeing up does not enable a sufferer to cope with the second working memory difficulty - as Raalten says - they do not hold on one side an intention that they will want to proceed with later on, a memory intention that will need attention later on. [ this prospective memory process seems to involve linking [ 3. Gold ] without sufficient of that capacity , lodged experience cannot be updated to take account of what is going on now, that needs to be taken into account, and where necessary corrected. three other brain areas - according to whatever background has to be attended to, and dealt with, along the way. But the hippocampus is involved as part of the linking within the grouping, so that any prospective intention is thwarted [ A well functioning patient in a well settled active routine - gardening for others, nationally recognised photography, skilful work with wood, regularly driving forty miles two or three times a week to help out an ex hospital acquaitance, steadily busy with this during the last ten years, twenty-five years with the illness - a carer ... " I had quite a long discussion with X. re: reading which he has just started again having always read quite a lot before the onset of illness. He got a copy of "The Woodlanders" which he had read as a school project. He told me that he had great difficulty in connecting the characters with the descriptions intervening. He got lost in trying to recall the top of a page with what was going on at the bottom. [ It's a prospective memory task - trying to keep up with a fictional narrative requires holding a lot of background whilst moving forward ] He had found the same with other books he had tried to read. He also finds that any disturbance affects his ability to retain anything he has started out on." Another prospectibve challenge :- To test their hypothesis researchers [Elvevaag ], based at NIMH and at the University of Warwick, compared the prospective memory of people with and without the disease. In each test participants manoeuvred a ball around an obstacle course for 90 seconds. The ongoing activity was a commercial battery-powered game ("Kongman"; TOMY Toy Corporation, 1982) in which a steel ball was to be moved around an obstacle course by pressing a button at the appropriate time points in order to open or close certain routes through which the ball could travel. Each game lasted 90 seconds, and participants were instructed to accumulate as many points as possible during each game until the time was up. The Game commenced by each participant winding a timer at the base of the game. The game was sufficiently easy and enjoyable that participants engaged in the game and all participants performed extremely well. [ i.e. the Study subjects with schizophrenia had rehearsed and so 'chunked' the game, and then did well on the basic test ... but then ...later ... ] During the course of the game the timer moved from the start to the finish position ( taking 90 seconds ). The rim surround of the timer was covered and colored with red and green colored paper, such that the first 25 seconds were red and the remaining 65 seconds green. The Prospective Memory task was to turn a counter (a poker chip that was similar on both sides) over once during each game. However, participants were instructed to turn the counter over only when the timer reached the green zone (i.e., they could not respond prospectively immediately, but had to wait for some proportion of time into the game before responding). were to play the game a total of 10 times (i.e., 10 trials). After each of the ten games, participants were asked if they had remembered to turn the counter over during the game. The experimenter employed a stopwatch to note the time at which the counter was turned over, and whether it was in the green or red zone. The participants' response to the question concerning whether they remembered to turn over the counter was also noted. They were then asked [ the holding injunction ] to turn over a counter when they were at least 25 seconds into the test. The time delay ensured that prospective [ i.e. recall for a future event ] memory had to be used. Participants with schizophrenia were more likely to forget to turn over the counter. At the end of the test the participants were asked if they had remembered to turn over the counter. Approximately a third of the time participants with schizophrenia reported they had done so when they had not.

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References :-

.
stem cell proliferation is decreased in schizophrenia, but not in depression<br> A Reif1,4, S Fritzen,4, M Finger, A Strobel, M Lauer, A SchmittK-P Lesch Molecular Psychiatry (2006) 11, 514–522

.
Automatization and working memory capacity in schizophrenia<br> Tamar R. van Raalten a,?, Nick F. Ramsey , J. Martijn Jansma , Gerry Jager a, Renι S. Kahn / Schizophrenia Research 100 (2008) 161–171

.
Reduced capacity but spared precision and maintenance of working memory representations in schizophrenia
JM Gold, Ph.D., Hahn, Ph.D., Zhang, Ph.D. Robinson, , Kappenman, , Beck, , and Luck, Ph.D. Arch Gen Psychiatry. 2010 June ; 67(6): 570–577.

.
Neurogenesis in the human hippocampus and its relevance to temporal lobe epilepsies
Florian A. Siebzehnrubl and Ingmar Blumcke Epilepsia, 49(Suppl. 5):55–65, 2008

8.Measuring memory impairment in community-based patients with schizophrenia Al-UZRI et al:- B J PSYCHIATRY 2006 189 132-13

7. CIARA KELLY, VAL SHARKEY, GARY MORRISON, JUDITH ALLARDYCE, and ROBIN G. McCREADIE The British Journal of Psychiatry 2000 v. 177, p. 348-353.

.
targeting of the CA1 sub- field of the hippocampus by schizophrenia and related psychotic disorders.
Scott A. Schobel; Nicole M. Lewandowski; Cheryl M. Corcoran; Holly Moore; Truman Brown; Dolores Malaspina; Scott A. Small Arch Gen Psychiatry. 2009;66(9):938-946.

.
Psychiatry [ research article open access ]
Habitual prospective memory in schizophrenia
Brita Elvevaag, Elizabeth A Maylor, Abigail L Gilbert
is available from: http://www.biomedcentral.com/1471-244X/3/9

back to home page

Is this what happens - early damage followed by a later 'releaser gene' causing further damage in late adolescence and after
Teng KY et al Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA.

Animals with a neonatal ventral hippocampal lesion (NVHL) develop abnormal behaviors during or after adolescence,
suggesting that early insults can have delayed consequences.

Recognise that when the illness strikes the person with schizophrenia is left to cope with whatever level of personal, domestic, work , and experience in relationships that they possessed at the time the illness struck.

They do not easily move on from their own efforts. Without enough working memory the whole system of calling upon memory is interrupted. Seeing and realising a prospect beyond a simple short term will be too difficult, except sometimes where there is already a preserved body of practical knowledge and interest in a particular area before the illness struck.
They can connect to a programme of activities in the day and week once they have been helped into it, in increments -'chunking'.

But something remains unexplained
that this study leaves for further understanding.

[ this prospective memory process seems to involve linking three other brain areas - according to whatever background has to be attended to, and dealt with, along the way.
But the hippocampus is involved as part of the linking within the grouping, so that any prospective intention is thwarted

[ A well functioning patient in a well settled active routine - gardening for others, nationally recognised photography, skilful work with wood, regularly driving forty miles two or three times a week to help out an ex hospital acquaintance, steadily busy with this during the last ten years, twenty-five years with the illness -

a carer ... " I had quite a long discussion with X. re: reading which he has just started again having always read quite a lot before the onset of illness.
He got a copy of "The Woodlanders" which he had read as a school project.
He told me that he had great difficulty in connecting the characters with the descriptions intervening. He got lost in trying to recall the top of a page with what was going on at the bottom. [ It's a prospective memory task - trying to keep up with a fictional narrative requires holding a lot of background whilst moving forward ]
He had found the same with other books he had tried to read.
He also finds that any disturbance affects his ability to retain anything he has started out on."

Another prospectibve challenge :-

To test their hypothesis researchers [Elvevaag ], based at NIMH and at the University of Warwick, compared the prospective memory of people with and without the disease.
In each test participants manoeuvred a ball around an obstacle course for 90 seconds.

The ongoing activity was a commercial battery-powered game ("Kongman"; TOMY Toy Corporation, 1982) in which a steel ball was to be moved around an obstacle course by pressing a button at the appropriate time points in order to open or close certain routes through which the ball could travel. Each game lasted 90 seconds, and participants were instructed to accumulate as many points as possible during each game until the time was up.

The Game commenced by each participant winding a timer at the base of the game. The game was sufficiently easy and enjoyable that participants engaged in the game and all participants performed extremely well.
[ i.e. the Study subjects with schizophrenia had rehearsed and so 'chunked' the game, and then did well on the basic test ... but then ...later ... ]

During the course of the game the timer moved from the start to the finish position ( taking 90 seconds ).
The rim surround of the timer was covered and colored with red and green colored paper, such that the first 25 seconds were red and the remaining 65 seconds green.

The Prospective Memory task was to turn a counter (a poker chip that was similar on both sides) over once during each game.
However, participants were instructed to turn the counter over only when the timer reached the green zone
(i.e., they could not respond prospectively immediately, but had to wait for some proportion of time into the game before responding).

were to play the game a total of 10 times (i.e., 10 trials). After each of the ten games, participants were asked if they had remembered to turn the counter over during the game. The experimenter employed a stopwatch to note the time at which the counter was turned over, and whether it was in the green or red zone. The participants' response to the question concerning whether they remembered to turn over the counter was also noted.

They were then asked [ the holding injunction ] to turn over a counter when they were at least 25 seconds into the test.

The time delay ensured that prospective [ i.e. recall for a future event ] memory had to be used.

Participants with schizophrenia were more likely to forget to turn over the counter.

At the end of the test the participants were asked if they had remembered to turn over the counter.

Approximately a third of the time participants with schizophrenia reported they had done so when they had not.

back to top

References :-

.
stem cell proliferation is decreased in schizophrenia, but not in depression<br> A Reif1,4, S Fritzen,4, M Finger, A Strobel, M Lauer, A SchmittK-P Lesch Molecular Psychiatry (2006) 11, 514–522

.
Automatization and working memory capacity in schizophrenia<br> Tamar R. van Raalten a,?, Nick F. Ramsey , J. Martijn Jansma , Gerry Jager a, Renι S. Kahn / Schizophrenia Research 100 (2008) 161–171

.
Reduced capacity but spared precision and maintenance of working memory representations in schizophrenia
JM Gold, Ph.D., Hahn, Ph.D., Zhang, Ph.D. Robinson, , Kappenman, , Beck, , and Luck, Ph.D. Arch Gen Psychiatry. 2010 June ; 67(6): 570–577.

.
Neurogenesis in the human hippocampus and its relevance to temporal lobe epilepsies
Florian A. Siebzehnrubl and Ingmar Blumcke Epilepsia, 49(Suppl. 5):55–65, 2008

8.Measuring memory impairment in community-based patients with schizophrenia J. Bruce, MBChB, MRCPsych, S. Frost, MBBS, MRCPsych and D. Mackintosh, MBChB, MRCPsych B J PSYCHIATRY 2006 189 132-13

7. CIARA KELLY, VAL SHARKEY, GARY MORRISON, JUDITH ALLARDYCE, and ROBIN G. McCREADIE The British Journal of Psychiatry 2000 v. 177, p. 348-353.

.
targeting of the CA1 sub- field of the hippocampus by schizophrenia and related psychotic disorders.
Scott A. Schobel; Nicole M. Lewandowski; Cheryl M. Corcoran; Holly Moore; Truman Brown; Dolores Malaspina; Scott A. Small Arch Gen Psychiatry. 2009;66(9):938-946.

.
Psychiatry [ research article open access ]
Habitual prospective memory in schizophrenia
Brita Elvevaag, Elizabeth A Maylor, Abigail L Gilbert
is available from: http://www.biomedcentral.com/1471-244X/3/9

back to home page

There are developments now in new techniques to study the level of neurogenesis activity in the living ....

Manganas:- Science 318 980-985 2007

" In our work, we identified a spectroscopic biomarker of NPCs,
developed a methodology to detect this biomarker in the live brain,
and demonstrated the use of the biomarker for identifying NPCs [ Neural Precursor Cells = maturing to stem cells ] in the live human brain.

The NPC biomarker could be readily detected in vitro with 1H-NMR,
but its detection at low concentrations in the live brain with 1H-MRS
required the development of more refined methodology.

Our SVD-based signal processing proved to be superior to the traditionally used Fourier transform
and can now be applied in a variety of imaging settings where low levels of a particular metabolite preclude its reliable detection in vivo.

Our results suggest that the NPC biomarker, represented by a 1.28-ppm spectral peak, is a complex mixture of saturated and/or monounsaturated fatty acids and related compounds.

The functional relevance of these molecules for the control of proliferation and differentiation of NPCs remains to be elucidated.

Finally, our data on humans provide in vivo imaging evidence for NPCs in the human hippocampus.

These findings support the numerous data demonstrating continuous neurogenesis in the dentate gyrus .
We also demonstrated that in humans the presence of the NPC biomarker in the hippocampus dramatically decreases with age.
Although a decrease in neurogenesis has been reported in aging mammals,
these are the first data from the living human brain that indicate a decrease in NPCs during brain development from childhood to adulthood.
A shame the study did not record results in the age range 17- 24
- reckoned to be the highest level for adult neurogenesis ,and a critical age for starting schizophrenia.
The normal age range for this period will be necessary for any before/after neurogenesis change in schizophrenia.
More generally, this biomarker can be applied to track and analyze endogenous or transplanted NPCs,
to monitor neurogenesis in a wide range of human neurological and psychiatric disorders,
and to evaluate the efficiency of therapeutic interventions. "

9.

Ana C. Pereira et al PNAS March 27, 2007 vol. 104 no. 13 5643

With continued debate over the functional significance of adult neurogenesis,
identifying an in vivo correlate of neurogenesis has become an important goal.

Here we rely on the coupling between neurogenesis and angiogenesis
and test whether MRI measurements of cerebral blood volume (CBV) provide an imaging correlate of neurogenesis.

First, we used an MRI approach to generate CBV maps over time in the hippocampal formation of exercising mice.
Among all hippocampal subregions, exercise was found to have
a primary effect on dentate gyrus CBV, the only subregion that supports adult neurogenesis.
Moreover, exercise-induced increases in dentate gyrus CBV
were found to correlate with postmortem measurements of neurogenesis.

Second, using similar MRI technologies, we generated CBV maps over time in the hippocampal formation of exercising humans.
As in mice, exercise was found to have a primary effect on dentate gyrus CBV, and the CBV changes were found to selectively correlate with cardiopulmonary and cognitive function.

Taken together, these findings show that dentate gyrus CBV provides an imaging correlate of exercise-induced neurogenesis
and that exercise differentially targets the dentate gyrus,
a hippocampal subregion important for memory and implicated in cognitive aging..

10.
Clinical Brain Disorders Branch, Intramural Research Programs, National Institute of Mental Health, 10 Center Drive, Room 4S235 MSC 1379, Bethesda, MD 20892-1379 Abstract Physiological Characteristics of Capacity Constraints in Working Memory as Revealed by Functional MRI

fundamental characteristic of working memory is that its capacity to handle information is limited.

While there have been many brain mapping studies of working memory, the physiological basis of its capacity limitation has not been explained.
We identified characteristics of working memory capacity using functional magnetic resonance imaging (fMRI) in healthy subjects.
Working memory capacity was studied using a parametric 'n-back' working memory task involving increasing cognitive load and ultimately decreasing task performance.
Loci within dorsolateral prefrontal cortex (DLPFC) evinced exclusively an 'inverted-U' shaped neuro- physiological response
from lowest to highest load, consistent with a capacity-constrained response.

Regions outside of DLPFC, in contrast, were more heterogeneous in response and often showed
early plateau or continuously increasing responses, which did not reflect capacity constraints.

However, sporadic loci, including in the premotor cortex, thalamus and superior parietal lobule, also demonstrated putative capacity-constrained responses,
perhaps arising as an upstream effect of DLPFC limitations or as part of a broader network-wide capacity limitation.

These results demonstrate that regionally specific nodes within the working memory network are capacity-constrained in the physiological domain, providing a missing link in current explorations of the capacity characteristics of working memory.

mazhari et al Psychiat Res 179:253 ( 2010 )
Pieper et al Cell 142 39-51 July 2010
sieb Epilepsia 49 (suppl 5) 55-65 2008
References :- 1. Neural stem cell proliferation is decreased in schizophrenia, but not in depression
A Reif1,4, S Fritzen,4, M Finger, A Strobel, M Lauer, A SchmittK-P Lesch Molecular Psychiatry (2006) 11, 514–522 2. Automatization and working memory capacity in schizophrenia
Tamar R. van Raalten a,?, Nick F. Ramsey , J. Martijn Jansma , Gerry Jager a, Renι S. Kahn / Schizophrenia Research 100 (2008) 161–171 3. Reduced capacity but spared precision and maintenance of working memory representations in schizophrenia JM Gold, Ph.D.1, Hahn, Ph.D.1,a, Zhang, Ph.D.2,a, Robinson, B.A.1, Kappenman, M.A.2, Beck, B.A.2, and Luck, Ph.D.2Arch Gen Psychiatry. 2010 June ; 67(6): 570–577. 4. Neurogenesis in the human hippocampus and its relevance to temporal lobe epilepsies Florian A. Siebzehnrubl and Ingmar Blumcke Epilepsia, 49(Suppl. 5):55–65, 2008 5. Differential targeting of the CA1 sub- field of the hippocampus by schizophrenia and related psychotic disorders. Scott A. Schobel; Nicole M. Lewandowski; Cheryl M. Corcoran; Holly Moore; Truman Brown; Dolores Malaspina; Scott A. Small Arch Gen Psychiatry. 2009;66(9):938-946. 6.BMC Psychiatry [ research article open access ] ..... elvevaag et al Habitual prospective memory in schizophrenia Brita Elvevaag, Elizabeth A Maylor, Abigail L Gilbert article is available from: http://www.biomedcentral.com/1471-244X/3/9

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