of goldman-rakic and others showed that principal sulcal, dorsolateral pfc interconnects with all of these brain regions, and that neuronal microcircuits within pfc are able to maintain information in working memory through recurrent excitatory glutamate networks of pyramidal cells that continue to fire throughout the delay period. these circuits are tuned by lateral inhibition from gabaergic interneurons. the neuromodulatory arousal systems markedly alter pfc working memory function; for example, either too little or too much dopamine or norepinephrine impairs pfc network firing and working memory performance. the research described above on persistent firing of certain neurons in the delay period of working memory tasks shows that the brain has a mechanism of keeping representations active without external input. keeping representations active, however, is not enough if the task demands maintaining more than one chunk of information. in addition, the components and features of each chunk must be bound together to prevent them from being mixed up. for example, if a red triangle and a green square must be remembered at the same time, one must make sure that "red" is bound to "triangle" and "green" is bound to "square". one way of establishing such bindings is by having the neurons that represent features of the same chunk fire in synchrony, and those that represent features belonging to different chunks fire out of sync. in the example, neurons representing redness would fire in synchrony with neurons representing the triangular shape, but out of sync with those representing the square shape. so far, there is no direct evidence that working memory uses this binding mechanism, and other mechanisms have been proposed as well. it has been speculated that synchronous firing of neurons involved in working memory oscillate with frequencies in the theta band (4 to 8 hz). indeed, the power of theta frequency in the eeg increases with working memory load, and oscillations in the theta band measured over different parts of the skull become more coordinated when the person tries to remember the binding between two components of information. localization in the brain localization of brain functions in humans has become much easier with the advent of brain imaging methods (pet and fmri). this research has confirmed that areas in the pfc are involved in working memory functions. during the 1990s much debate has centered on the different functions of the ventrolateral (i.e., lower areas) and the dorsolateral (higher) areas of the pfc. a human lesion study provides additional evidence for the role of the dorsolateral prefrontal cortex in working memory. one view was that the dorsolateral areas are responsible for spatial working memory and the ventrolateral areas for non-spatial working memory. another view proposed a functional distinction, arguing that ventrolateral areas are mostly involved in pure maintenance of information, whereas dorsolateral areas are more involved in tasks requiring some processing of the memorized material. the debate is not entirely resolved but most of the evidence supports the functional distinction. brain imaging has revealed that working memory functions are not limited to the pfc. a review of numerous studies shows areas of activation during working memory tasks scattered over a large part of the cortex. there is a tendency for spatial tasks to recruit more right-hemisphere areas, and for verbal and object working memory to recruit more left-hemisphere areas. the activation during verbal working memory tasks can be broken down into one component reflecting maintenance, in the left posterior parietal cortex, and a component reflecting subvocal rehearsal, in the left frontal cortex (broca's area, known to be involved in speech production). there is an emerging consensus that most working memory tasks recruit a network of pfc and parietal areas. a study has shown that during a working memory task the connectivity between these areas increases. another study has demonstrated that these areas are necessary for working memory, and not simply activated accidentally during working memory tasks, by temporarily blocking them through transcranial magnetic stimulation (tms), thereby producing an impairment in task performance. a current debate concerns the function of these brain areas. the pfc has been found to be active in a variety of tasks that require executive functions. this has led some researchers to argue that the role of pfc in working memory is in controlling attention, selecting strategies, and manipulating information in working memory, but not in maintenance of information. the maintenance function is attributed to more posterior areas of the brain, including the parietal cortex. other authors interpret the activity in parietal cortex as reflecting executive functions, because the same area is also activated in other tasks requiring attention but not memory. a 2003 meta-analysis of 60 neuroimaging studies found left frontal cortex was involved in low-task demand verbal working memory and right frontal cortex for spatial working memory. brodmann's areas (bas) 6, 8, and 9, in the superior frontal cortex was involved when working memory must be continuously updated and when memory for temporal order had to be maintained. right brodmann 10 and 47 in the ventral frontal cortex were involved more frequently with demand for manipulation such as dual-task requirements or mental operations, and brodmann 7 in the posterior parietal cortex was also involved in all types of executive function. working memory has been suggested to involve two processes with different neuroanatomical locations in the frontal and parietal lobes. first, a selection operation that retrieves the most relevant item, and second an updating operation that changes the focus of attention made upon it. updating the attentional focus has been found to involve the transient activation in the caudal superior frontal sulcus and posterior parietal cortex, while increasing demands on selection selectively changes activation in the rostral superior frontal sulcus and posterior cingulate/precuneus. articulating the differential function of brain regions involved in working memory is dependent on tasks able to distinguish these functions. most brain imaging studies of working memory have used recognition tasks such as delayed recognition of one or several stimuli, or the n-back task, in which each new stimulus in a long series must be compared to the one presented n steps back in the series. the advantage of recognition tasks is that they require minimal movement (just pressing one of two keys), making fixation of the head in the scanner easier. experimental research and research on individual differences in working memory, however, has used largely recall tasks (e.g., the reading span task, see below). it is not clear to what degree recognition and recall tasks reflect the same processes and the same capacity limitations. brain imaging studies have been conducted with the reading span task or related tasks. increased activation during these tasks was found in the pfc and, in several studies, also in the anterior cingulate cortex (acc). people performing better on the task showed larger increase of activation in these areas, and their activation was correlated more over time, suggesting that their neural activity in these two areas was better coordinated, possibly due to stronger connectivity. neural models one approach to modeling the neurophysiology and the functioning of working memory is prefrontal cortex basal ganglia working memory (pbwm). in this model, the prefrontal cortex works hand-in-hand with the basal ganglia to accomplish the tasks of working memory. many studies have shown this to be the case. one used ablation techniques in patients who had had seizures and had damage to the prefrontal cortex and basal ganglia. researchers found that such damage resulted in decreased capacity to carry out the executive function of working memory. additional research conducted on patients with brain alterations due to methamphetamine use found that training working memory increases volume in the basal ganglia. effects of stress on neurophysiology working memory is impaired by acute and chronic psychological stress. this phenomenon was first discovered in animal studies by arnsten and colleagues, who have shown that stress-induced catecholamine release in pfc rapidly decreases pfc neuronal firing and impairs working memory performance through feedforward, intracellular signaling pathways. exposure to chronic stress leads to more profound working memory deficits and additional architectural changes in pfc, including dendritic atrophy and spine loss, which can be prevented by inhibition of protein kinase c signaling. fmri research has extended this research to humans, and confirms that reduced working memory caused by acute stress links to reduced activation of the pfc, and stress increased levels of catecholamines. imaging studies of medical students undergoing stressful exams have also shown weakened pfc functional connectivity, consistent with the animal studies. the marked effects of stress on pfc structure and function may help to explain how stress can cause or exacerbate mental illness. the more stress in one's life, the lower the efficiency of working memory in performing simple cognitive tasks. students who performed exercises that reduced the intrusion of negative thoughts showed an increase in their working memory capacity. mood states (positive or negative) can have an influence on the neurotransmitter dopamine, which in turn can affect problem solving. effects of alcohol on neurophysiology excessive alcohol use can result in brain damage which impairs working memory. alcohol has an effect on the blood-oxygen-level-dependent (bold) response. the bold response correlates increased blood oxygenation with brain activity, which makes this response a useful tool for measuring neuronal activity. the bold response affects regions of the brain such as the basal ganglia and thalamus when performing a working memory task. adolescents who start drinking at a young age show a decreased bold response in these brain regions. alcohol dependent young women in particular exhibit less of a bold response in parietal and frontal cortices when performing a spatial working memory task. binge drinking, specifically, can also affect one's performance on working memory tasks, particularly visual working memory. additionally, there seems to be a gender difference in regards to how alcohol affects working memory. while women perform better on verbal working memory tasks after consuming alcohol compared to men, they appear to perform worse on spatial working memory tasks as indicated by less brain activity. finally, age seems to be an additional factor. older adults are more susceptible than others to the effects of alcohol on working memory. genetics behavioral genetics individual differences in working-memory capacity are to some extent heritable; that is, about half of the variation between individuals is related to differences in their genes. the genetic component of variability of working-memory capacity is largely shared with that of fluid intelligence. attempts to identify individual genes little is known about which genes are related to the functioning of working memory. within the theoretical framework of the multi-component model, one candidate gene has been proposed, namely robo1 for the hypothetical phonological loop component of working memory. more recently another gene was found regarding working memory. looking at genetically diverse mice, gpr12 was found in promoting a protein necessary for working memory. when they took mice that were performing worse on memory tests than their control mouse counterparts and increased their gpr12 proteins, those mice improved from 50% to 80%. that brought the low performance mice up to level similar to their control counterparts. with the build up of prior work on mice such as testing the formimidoyltransferase cyclodeaminase (ftcd) gene in regards to the morris water maze performance, testing out if there was a potential variation of genetic coding within the ftcd gene within humans was soon tested out. results showed that a variation was found but varied depending on the age of the individual. in regards to the ftcd gene, it appeared that only children were affected by it. working memory seemed to have a higher performance when the ftcd gene was present but had no similar affect to adults. role in academic achievement working memory capacity is correlated with learning outcomes in literacy and numeracy. initial evidence for this relation comes from the correlation between working-memory capacity and reading comprehension, as first observed by daneman and carpenter (1980) and confirmed in a later meta-analytic review of several studies. subsequent work found that working memory performance in primary school children accurately predicted performance in mathematical problem solving. one longitudinal study showed that a child's working memory at 5 years old is a better predictor of academic success than iq. a randomized controlled study of 580 children in germany indicated that working memory training at age six had a significant positive effect in spatial working memory immediately after training,