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A wide range of human activities are performed sequentially in few seconds. We need to maintain a correct temporal order of words in language, movements in actions, directions in navigation, etc. Therefore, it is plausible, in a more economical perspective, that our brain is equipped with a dedicated mechanism for storing a temporal sequence for a short time. To investigate it, we run four TMS experiments, in which participants performed different short-term memory tasks, i.e., three (verbal, spatial, motor) requiring maintenance of an ordered sequence and one (visual) of a static pattern. We demonstrated, for the first time, that the left supramarginal gyrus is one of the key nodes of the STM network involved in retaining an abstract representation of serial order information, independently from the content information, namely the nature of the item to be remembered, which instead is stored separately.

Prism adaptation (PA) has proven to be effective in alleviating many signs of unilateral spatial neglect (USN). Generally, the principal improvement after PA treatment was found to be in the high-level cognitive function. Nevertheless, some evidence has also been found for it in somatosensory function. We have aimed to test the influence of PA on neglect hemianesthesia, a condition in which the high-level neglect-related deficit mimics hemianesthesia. Twenty-one USN patients were enrolled in the study. Each patient performed two sessions of PA, one with neutral glasses and one with prism glasses using a cross-over design. Sensitivity on the upper limb was tested using two methods. The first task was the sensibility subtest which was derived from the standard clinical examination. The second was the perceptual and motor electro-cutaneous threshold on the forearms using an electro-cutaneous stimulator. Four neuropsychological tests were used to diagnose USN and to check improvement: Star cancellation, Line bisection, Sentence reading and the Comb & Razor test. Comparing prism with sham conditions, our results show significant improvements in double extinction and in the electro-cutaneous perceptual threshold only for the contralesional hand. No improvement was found for the ipsilesional hand, for the motor threshold, and for neutral glasses. Significant improvement was found in personal neglect. Replication of the task in a subgroup of patients confirmed the primary results. The improvements in somatosensory perception together with the amelioration of personal neglect suggest that PA also has a specific effect on the neglect hemianesthesia.

Neuropsychological data about acquired impairments in reading and writing provide a strong basis for the theoretical framework of the dual-route models. The present study explored the functional neuroanatomy of the reading and spelling processing system. We describe the reading and writing performance of patient CF, an Italian native speaker who developed an extremely selective reading and spelling deficit (his spontaneous speech, oral comprehension, repetition and oral picture naming were almost unimpaired) in processing double letters associated with surface dyslexia and dysgraphia, following a tumor in the left temporal lobe. In particular, the majority of CF's errors in spelling were phonologically plausible substitutions, errors concerning letter numerosity of consonants, and syllabic phoneme-to-grapheme conversion (PGC) errors. A similar pattern of impairment also emerged in his reading behavior, with a majority of lexical stress errors (the only possible type of surface reading errors in the Italian language, due the extreme regularity of print-to-sound correspondence). CF's neuropsychological profile was combined with structural neuroimaging data, fiber tracking, and functional maps and compared to that of healthy control participants. We related CF's deficit to a dissociation between impaired ventral/lexical route (as evidenced by a fractional anisotropy - FA decrease along the inferior fronto-occipital fasciculus - IFOF) and relatively preserved dorsal/phonological route (as evidenced by a rather full integrity of the superior longitudinal fasciculus - SLF). In terms of functional processing, the lexical-semantic ventral route network was more activated in controls than in CF, while the network supporting the dorsal route was shared by CF and the control participants. Our results are discussed within the theoretical framework of dual-route models of reading and spelling, emphasize the importance of the IFOF both in lexical reading and spelling, and offer a better comprehension of the neurological and functional substrates involved in written language and, in particular, in surface dyslexia and dysgraphia and in doubling/de-doubling consonant sounds and letters.

Neuropsychological Laboratory, IRCCS Istituto Auxologico Italiano, Milano, ItalyA few years ago a brief communication on Nature reportedlearning-induced plasticity in the gray matter of the brains ofvolunteers who had learned to juggle (Draganski et al., 2004).These individuals showed a transient and selective structuralchange in brain areas associated with the processing andstorage of complex visual motion. This discovery of astimulus-dependent alteration in the brain's macroscopicstructure contradicted the traditional, and at that time pre-vailing, view that cortical plasticity is associated with func-tional, rather than anatomical, changes (Draganski & May,2008). This finding gave also impetus to the study of neuro-plasticity, suggesting that in the gray matter not only reduc-tion of volume is possible, such as in ageing, but alsoincrement. There may be, however, some abuse of the term“neuroplasticity” (used with “gay abandon”, as suggested byBuchtel, 1978). Following Paillard (see Will, Dalrymple-Alford,Wolff, & Cassel, 2008), changes in the nervous system shouldbe called “plastic” only when the connectivity network of thesystem undergoes lasting changes in the structure that linkstogether its elements. Furthermore, changes,to be considered“plastic”, should be both structural and functional, namelyonly when a given system (here, a set of cortico-subcorticalnetworks) achieves a novel function, either by transformingits pattern of internal connectivity, or by changing the ele-ments of which it is made, or both. Random (backgroundnoise) and systematic variations, namely, operating errorsbeyond the flexibility of the system, as well as vicariousstrategies used to achieve a given behavioral goal should notbe regarded as plastic changes. With reference to the life spanof the living organism, the distinction may be drawn betweenthe structural malleability of the system during development,within the range of genetic competence (termed by Paillardgenetic plasticity), and the capacity of the fully developed sys-tem to change its own structure, and to expand its behavioralrepertoire, namely: the adaptive plasticity of a system whichhas already completed its maturation. The possibility that agiven neural system achieves a novel function does notnecessarily mean that the functional (psychological, cogni-tive) architecture changes. The function may be “novel”, withreference to the previous activity of that neural network, butnot per se, namely: the plastic system may replace, at least inpart, another damaged network, taking over and maintainingthe functional properties of the latter. This is a key assump-tion, in order to make meaningful inferences from the path-ological behavior of brain-damaged patients to the functionalorganizationofthenormalsystem(discussioninVallar,2000).Finally,plasticityreferstoachangeinstructureinresponsetoan external force, and the maintenance of that shape afterremoval of the force, in contrast to “elasticity”, which impliesthe return to the previous form, when the force is removed(Berlucchi & Buchtel, 2009).While convincing empirical evidence suggesting thatplastic changes may occur in the brain is quite recent, therootsof the conceptof “neuroplasticity” maybe tracedback tothe second half of the XIX century. Berlucchi and Buchtel(2009) pointed out that the Italian psychiatrist ErnestoLugaro (1870e1940) was the first to introduce the term “plas-ticity” (also used by the North American psychologist WilliamJames,todenotechangesinnervouspathsassociatedwiththeestablishment of habits) in order to link neuroplasticity tosynaptic plasticity as early as 1906. By this term Lugaro meantthat the anatomoefunctional relations between neuronsmight change in an adaptive way along our life span, in orderto allow psychic maturation, learning, as well as functionalrecovery after brain damage. Lugaro's concept of plasticitywas inspired by a neural hypothesis of learning and memoryput forward in 1893 by his mentor Eugenio Tanzi, whopostulated that practice and experience promote neuronalgrowth and identified the articulation between neurons assites of neural plasticity. Cajal (references in Berlucchi &

Semantic fluency is widely used both as a clinical test and as a basic tool for understanding how humans extract information from the semantic store. Recently, major efforts have been made to devise fine-grained scoring procedures to measure the multiple cognitive processes underlying fluency performance. Nevertheless, it is still unclear how many and which independent components are necessary to thoroughly describe performance on the fluency task. Furthermore, whether a combination of multiple indices can improve the diagnostic performance of the test should be assessed. In this study, we extracted multiple indices of performance on the semantic fluency test from a large sample of healthy controls (n = 307) and patients (n = 145) suffering from three types of focal dementia or Alzheimer's Disease (AD). We found that five independent components underlie semantic fluency performance. We argue that these components functionally map onto the generation and application of a search strategy (component 2), to the monitoring of the overall sequence to avoid repetitions (component 3) and out-of-category items (component 4), and to the full integrity of the semantic store (component 5). The integrated and effective work of all these components would relate to a “general effectiveness” component (component 1). Importantly, while all the focal dementia groups were equally impaired on general effectiveness measures, they showed differential patterns of failure in the other components. This finding suggests that the cognitive deficit that impairs fluency differs among the three focal dementia groups: a semantic store deficit in the semantic variant of primary progressive aphasia (sv-PPA), a strategy deficit in the non-fluent variant of primary progressive aphasia (nfv-PPA), and an initiation deficit in the behavioural variant of fronto-temporal dementia (bv-FTD). Finally, we showed that the concurrent use of multiple fluency indices improves the diagnostic accuracy of semantic fluency both for focal dementias and for AD. More generally, our study suggests that a formal evaluation of fine-grained patterns of performance would improve the diagnostic accuracy of neuropsychological tests.

Perseveration in target cancellation tasks and in drawing by copy and from memory was investigated in 21 right-brain-damaged patients, seven with no evidence of left visuo-spatial neglect, and 14 with neglect. Eight such neglect patients showed perseveration in both cancellation and drawing tasks, although no correlation was found with the severity of neglect. Patients with perseveration were not disproportionately impaired in tasks assessing executive (fluency, Stroop colour-word interference, and Weigl's sorting test), and visuo-spatial short-term memory function. In the context of a two-component hypothesis, graphic perseveration (the first component) is a specific disorder that manifests in a variety of tasks, particularly those requiring serial graphic production. Unilateral spatial neglect (the second component) may trigger and facilitate the production of perseveration errors, with a contra-ipsilateral gradient of increasing severity.

In the present paper we report the performance on object use and on semantic tasks of two patients, D.L. with probable semantic dementia, and A.M. with an atypical onset of dementia of Alzheimer, assessed twice two years apart. In particular, we investigated whether the patients' ability to use objects degraded as a function of their semantic knowledge about those objects. Results from the two assessments in 2002 and in 2004 confirmed that both patients had a selective loss of the lexical-semantic knowledge, despite a relative preservation of the other cognitive abilities including object use. This pattern of results suggests that semantic knowledge is not necessarily involved in the correct use of objects.

The effects of adaptation to prisms displacing rightwards the field of vision on omission errors, and on perseveration and other graphic productions in a line cancellation task, were assessed in nine right-brain-damaged patients with left unilateral spatial neglect. Prism adaptation improved both neglect, as indexed by omission errors, and perseveration behaviour, up to a delay of 60 min. No correlation was found between omission and perseveration errors in all assessments. The suggestion is made that perseveration and other complex graphic productions made by right brain-damaged-patients with left spatial unilateral neglect is due to a defective monitoring of complex motor behaviour, frequently associated to cerebral damage involving the right frontal lobe. Interpretations of perseveration behaviour in terms of allochiria and directional hypokinesia are considered, and their limits discussed.