Publisher Summary This chapter focuses on the modern notion of short-term memory, called working memory. Working memory refers to the temporary maintenance of information that was just experienced or just retrieved from long-term memory but no longer exists in the external environment. These internal representations are short-lived, but can be maintained for longer periods of time through active rehearsal strategies, and can be subjected to various operations that manipulate the information in such a way that makes it useful for goal-directed behavior. Working memory is a system that is critically important in cognition and seems necessary in the course of performing many other cognitive functions, such as reasoning, language comprehension, planning, and spatial processing. This chapter demonstrates the functional importance of dopamine to working memory function in several ways. Elucidation of the cognitive and neural mechanisms underlying human working memory is an important focus of cognitive neuroscience and neurology for much of the past decade. One conclusion that arises from research is that working memory, a faculty that enables temporary storage and manipulation of information in the service of behavioral goals, can be viewed as neither a unitary, nor a dedicated system. Data from numerous neuropsychological and neurophysiological studies in animals and humans demonstrates that a network of brain regions, including the prefrontal cortex, is critical for the active maintenance of internal representations.

Chapter 11 Working memory

Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268

Thirty years of brain imaging research has converged to define the brain’s default network—a novel and only recently appreciated brain system that participates in internal modes of cognition Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations These two subsystems converge on important nodes of integration including the posterior cingulate cortex The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer’s disease

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The Brain's Default Network Anatomy, Function, and Relevance to Disease

During performance of attention-demanding cognitive tasks, certain regions of the brain routinely increase activity, whereas others routinely decrease activity. In this study, we investigate the extent to which this task-related dichotomy is represented intrinsically in the resting human brain through examination of spontaneous fluctuations in the functional MRI blood oxygen level-dependent signal. We identify two diametrically opposed, widely distributed brain networks on the basis of both spontaneous correlations within each network and anticorrelations between networks. One network consists of regions routinely exhibiting task-related activations and the other of regions routinely exhibiting task-related deactivations. This intrinsic organization, featuring the presence of anticorrelated networks in the absence of overt task performance, provides a critical context in which to understand brain function. We suggest that both task-driven neuronal responses and behavior are reflections of this dynamic, ongoing, functional organization of the brain.

https://www.pnas.org/content/pnas/102/27/9673.full.pdf

The human brain is intrinsically organized into dynamic, anticorrelated functional networks

Attention deficit hyperactivity disorder (ADHD) comprises a deficit in behavioral inhibition. A theoretical model is constructed that links inhibition to 4 executive neuropsychological functions that appear to depend on it for their effective execution: (a) working memory, (b) self-regulation of affect-motivation-arousal, (c) internalization of speech, and (d) reconstitution (behavioral analysis and synthesis). Extended to ADHD, the model predicts that ADHD should be associated with secondary impairments in these 4 executive abilities and the motor control they afford. The author reviews evidence for each of these domains of functioning and finds it to be strongest for deficits in behavioral inhibition, working memory, regulation of motivation, and motor control in those with ADHD. Although the model is promising as a potential theory of self-control and ADHD, far more research is required to evaluate its merits and the many predictions it makes about ADHD.

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Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD.

Visual drug cues are powerful triggers of craving in drug abusers contributing to enduring addiction. According to previous qualitative reviews, the response of the orbitofrontal cortex to such cues is sensitive to whether subjects are seeking treatment. Here we re-evaluate this proposal and assessed whether the nature of the drug matters. To this end, we performed a quantitative meta-analysis of 64 neuroimaging studies on drug-cue reactivity across legal (nicotine, alcohol) or illegal substances (cocaine, heroin). We used the ALE algorithm and a hierarchical clustering analysis followed by a cluster composition statistical analysis to assess the association of brain clusters with the nature of the substance, treatment status, and their interaction. Visual drug cues activate the mesocorticolimbic system and more so in abusers of illegal substances, suggesting that the illegal substances considered induce a deeper sensitization of the reward circuitry. Treatment status had a different modulatory role for legal and illegal substance abusers in anterior cingulate and orbitofrontal areas involved in inter-temporal decision making. The class of the substance and the treatment status are crucial and interacting factors that modulate the neural reactivity to drug cues. The orbitofrontal cortex is not sensitive to the treatment status per se, rather to the interaction of these factors. We discuss that these varying effects might be mediated by internal predispositions such as the intention to quit from drugs and external contingencies such as the daily life environmental availability of the drugs, the ease of getting them and the time frame of potential reward through drug consumption.

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How the harm of drugs and their availability affect brain reactions to drug cues: a meta-analysis of 64 neuroimaging activation studies

Several studies have shown age-related changes in motor imagery (MI) in older adults and the associated compensatory brain activation patterns; most of these studies have used explicit MI tasks or implicit MI tasks focused on mental rotation of body parts. Here, we address the effect of ageing on MI for the more complex visuomotor transformations entailed by mentally simulated hand-tool interactions triggered by a grip selection task (GST) for tools used in daily life. We studied 22 young and 22 elderly subjects performing the GST, in which they were asked to report whether they would grip a portrayed tool with an overhand or an underhand grip. We found a behavioral decline in the elderly group, accompanied by reduced activations of the left posterior parietal lobule, in a subregion associated specifically with reaching behavior by previous investigations. No differences were observed in the temporal cortices associated with object semantics. These results suggested a specific age-related vulnerability of the neural substrates, particularly for the imaginary reaching component of the task, rather than for the semantically driven grasping component. The combination of behavioral deficits and reduced activation of specific brain regions speaks in favor of a specific age-associated deficit for the complex imaginary movements required by the GST.

A Breakdown of Imagined Visuomotor Transformations and Its Neural Correlates in Young Elderly Subjects.

Gait control becomes more demanding in healthy older adults, yet what cognitive or motor process leads to this age-related change is unknown. The present study aimed to investigate whether it might depend on specific decay in the quality of gait motor representation and/or a more general reduction in the efficiency of lower limb motor control. Younger and older healthy participants performed in fMRI a virtual walking paradigm that combines motor imagery (MI) of walking and standing on the spot with the presence (Dynamic Motor Imagery condition, DMI) or absence (pure MI condition) of overtly executed ankle dorsiflexion. Gait imagery was aided by the concomitant observation of moving videos simulating a stroll in the park from a first-person perspective. Behaviorally, older participants showed no sign of evident depletion in the quality of gait motor representations, and absence of between-group differences in the neural correlates of MI. However, while younger participants showed increased frontoparietal activity during DMI, older participants displayed stronger activation of premotor areas when controlling the pure execution of ankle dorsiflexion, regardless of the imagery task. These data suggest that reduced automaticity of lower limb motor control in healthy older subjects leads to the recruitment of additional premotor resources even in the absence of basic gait functional disabilities.

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How aging affects the premotor control of lower limb movements in simulated gait.

On 15–16 November 2007 the University of Pavia, one of the oldest and most prestigious Italian Universities, hosted a meeting entitled “The Physiology of Mind” to celebrate the award of a “Laurea Honoris Causa” in Psychology to Giovanni Berlucchi. The meeting consisted of 25 invited lectures given by internationally renowned scientists who were intellectually related to Giovanni. Needless to say, the meeting was an astonishing success both for the scientiWc quality and the friendly, enthusiastic, atmosphere. The great majority of invited lecturers contributed a paper to this issue and others who chaired sessions were also invited to contribute. The result is a special issue of Experimental Brain Research, which eVectively captures the topic of the meeting, encompassing biological, physiological, neuropsychological and cognitive aspects of neuroscience. In other words, it reXects Giovanni Berlucchi’s wide range of interests and contributions to neuroscience. Giovanni begun his cultural adventure in neuroscience with a Medical Degree (“Laurea in Medicina e Chirurgia”) at the University of Pavia and was set to become a clinical neurologist. As was common among clever students at that time, however, he decided to get experience in basic research in neurophysiology before embarking on clinical work. An obvious choice was then to go to Pisa where Giuseppe Moruzzi headed a prestigious Institute of Physiology dedicated to research on the neural mechanisms of sleep and wakefulness. During his time in Pisa, in addition to engaging in various fruitful collaborations with Moruzzi, Giovanni became interested in Roger Sperry’s work and decided to go to Pasadena, California, to collaborate with Sperry at Caltech. This was the turning point in Giovanni’s career. On his return to Italy, he gave up the idea of becoming a clinical neurologist (to his father’s dismay—who was a well known academic neurologist) and started working in Pisa both on single-cell recordings in the cat’s visual system, following Hubel and Wiesel’s pioneering ideas, and on interhemispheric transmission with behavioural experiments in cats and humans. Thus, Clinical Neurology lost a probably excellent clinician but Physiology and Cognitive Neuroscience acquired a great scientist. The present issue is not formally divided into thematic sections but in fact contains contributions in six broadly deWned areas which roughly correspond to Giovanni’s range of interests. One topic which has been increasingly appealing to Giovanni in recent years is History of Neurobiology. Together with Gus Buchtel, Giovanni himself has contributed to this issue with a paper on the meaning and roots of the concept of “plasticity” in the nervous system. The paper brings to light original historic evidence, for example, that William James was the Wrst to use the term plasticity in reference to learning and the nervous system and also was the Wrst to distinguish between plastic changes related to modiWcation of existing pathways and those related to formation of new pathways. Interestingly, James’ ideas were developed before the discovery of the synapse by Sherrington. Also, the authors discuss the overlooked contribution to learning theories based on neuronal plasticity of the Italian neuropsychiatrists Tanzi and Lugaro. C. A. Marzi (&) Department of Neurological Sciences and Vision, University of Verona, Verona, Italy e-mail: carloalberto.marzi@univr.it

The physiology of mind.

Cross-cultural differences in normal and dyslexic reading: behavioural and functional anatomical observations in readers of regular and irregular orthographies

Eraldo Paulesu

Papers

How the harm of drugs and their availability affect brain reactions to drug cues: a meta-analysis of 64 neuroimaging activation studies

A Breakdown of Imagined Visuomotor Transformations and Its Neural Correlates in Young Elderly Subjects.

How aging affects the premotor control of lower limb movements in simulated gait.

The physiology of mind.

Cross-cultural differences in normal and dyslexic reading: behavioural and functional anatomical observations in readers of regular and irregular orthographies