False alarms during recognition of famous people from faces and voices in patients with unilateral temporal lobe resection and normal participants tested after anodal tDCS over the left or right ATL.

Data gathered in the field of the experimental social psychology have shown that it is more difficult to recognize a person through his/her voice than through his/her face and that false alarms (FA) are produced more in voice than in face recognition. Furthermore, some neuropsychological investigations have suggested that in patients with damage to the right anterior temporal lobe (ATL) the number of FA could be higher for voice than for face recognition. In the present study we assessed FA during recognition of famous people from faces and voices in patients with unilateral ATL tumours and in normal participants tested after anodal transcranial direct current stimulation (tCDS), over the left or right ATL. The number of FA was significantly higher in patients with right than in those with left temporal tumours on both face and voice familiarity. Furthermore, lesion side did not differentially affect patient's sensitivity or response criterion when recognizing famous faces, but influenced both these measures on a voice recognition task. In fact, in this condition patients with right temporal tumours showed a lower sensitivity index and a lower response criterion than those with left-sided lesions. In normal subjects, the greater right sided involvement in voice than in face processing was confirmed by the observation that right ATL anodal stimulation significantly increased voice but only marginally influenced face sensitivity. This asymmetry between face and voice processing in the right hemisphere could be due to the greater complexity of voice processing and to the difficulty of forming stable and well-structured representations, allowing to evaluate if a presented voice matches or not with an already known voice.

Investigating the functional neuroanatomy of concrete and abstract word processing through direct electric stimulation (DES) during awake surgery.

Neuropsychological, neuroimaging and electrophysiological studies demonstrate that abstract and concrete word processing relies not only on the activity of a common bilateral network but also on dedicated networks. The neuropsychological literature has shown that a selective sparing of abstract relative to concrete words can be documented in lesions of the left anterior temporal regions. We investigated concrete and abstract word processing in 10 patients undergoing direct electrical stimulation (DES) for brain mapping during awake surgery in the left hemisphere. A lexical decision and a concreteness judgment task were added to the neuropsychological assessment during intra-operative monitoring. On the concreteness judgment, DES delivered over the inferior frontal gyrus significantly decreased abstract word accuracy while accuracy for concrete words decreased when the anterior temporal cortex was stimulated. These results are consistent with a lexical-semantic model that distinguishes between concrete and abstract words related to different neural substrates in the left hemisphere.

Management of psychogenic non-epileptic seizures: a multidisciplinary approach.

The International League against Epilepsy (ILAE) proposed a diagnostic scheme for psychogenic non-epileptic seizure (PNES). The debate on ethical aspects of the diagnostic procedures is ongoing, the treatment is not standardized and management might differ according to age group. The objective was to reach an expert and stakeholder consensus on PNES management. A board comprising adult and child neurologists, neuropsychologists, psychiatrists, pharmacologists, experts in forensic medicine and bioethics as well as patients' representatives was formed. The board chose five main topics regarding PNES: diagnosis; ethical issues; psychiatric comorbidities; psychological treatment; and pharmacological treatment. After a systematic review of the literature, the board met in a consensus conference in Catanzaro (Italy). Further consultations using a model of Delphi panel were held. The global level of evidence for all topics was low. Even though most questions were formulated separately for children/adolescents and adults, no major age-related differences emerged. The board established that the approach to PNES diagnosis should comply with ILAE recommendations. Seizure induction was considered ethical, preferring the least invasive techniques. The board recommended looking carefully for mood disturbances, personality disorders and psychic trauma in persons with PNES and considering cognitive-behavioural therapy as a first-line psychological approach and pharmacological treatment to manage comorbid conditions, namely anxiety and depression. Psychogenic non-epileptic seizure management should be multidisciplinary. High-quality long-term studies are needed to standardize PNES management.

Defective recognition and naming of famous people from voice in patients with unilateral temporal lobe tumours.

Twenty-nine patients who underwent surgery for a temporal glioma, either in the left (16 patients) or right (13 patients) hemisphere, were administered standardized tests of unknown voice discrimination (UVD) and of famous voice recognition (VO-REC), which included tasks of familiarity evaluation, semantic identification and naming of famous voices. The UVD consisted of twenty stimuli, in which two audio files were consecutively presented; the subject was requested to judge whether the voices belonged to the same or different persons. In the VO-REC, patients were requested to recognize the voices of 40 very well known people; these voices were intermingled with the voices of 20 unknown people for a familiarity check, followed by identification and naming of persons recognized as familiar. We aimed at verifying the effect of laterality and intra-temporal site of lesion on familiarity assessment, false alarms, identification and naming of familiar people. As for the effect of lesion side, our results showed that patients with right temporal gliomas were significantly more impaired in voices discrimination and produced more false alarms than patients with a left glioma, who, in turn, were significantly more impaired in name retrieval than patients with a right temporal glioma. The high number of false alarms in patients with a right temporal glioma suggests that familiarity judgment was impaired. Regarding the neuroanatomical correlates of these different patterns of impairment, MRI data suggested that: (a) UVD disorders are due to lesions involving the whole right anterior temporal lobe and extending to lateral portions of the temporal and frontal lobes; (b) familiarity judgments (testified by an increased number of false alarms) are impaired in lesions restricted to the right anterior temporal lobe; (c) name retrieval deficits are found only in patients with left temporal lesions. UVD disorders were interpreted, at least in part, as due to an impairment of executive functions, resulting from a disconnection of the right temporal lobe from the frontal lobe control. A partly unexpected finding was that some patients with a right temporal tumour had a normal performance in famous voice recognition and identification, in spite of having severe voice discrimination disturbances. These unexpected results, in agreement with previous observation made in the visual (face) modality, are inconsistent with strictly hierarchical models of voice processing.

Neural correlates of the semantic interference effect: new evidence from transcranial direct current stimulation.

In two experiments, we combined a semantic blocked naming paradigm with anodal transcranial direct current stimulation (tDCS) to shed light on the neural correlates of the semantic interference (SI) effect. In particular, prior to the naming task, anodal tDCS was applied over the left superior temporal gyrus (STG, Experiment 1) or the left inferior frontal gyrus (IFG, Experiment 2) to enhance cortical excitability in these regions. In both experiments, participants were tested in two sessions in which either real or sham tDCS was delivered. We found that anodal tDCS over the left STG significantly increased the SI effect, whereas anodal tDCS over the left IFG led to a reduction of the SI effect. Overall, our data confirm the existence of a distributed cortical network involved in lexical retrieval and show that both the left IFG and the left STG play a causal role in this process. In particular, the left IFG is likely to be critical in resolving the conflict between competitor lexical representations, while the left STG seems to be the neural locus of the lexical representational system, where competition among different lexical representations occurs.

Literal, fictive and metaphorical motion sentences preserve the motion component of the verb: a TMS study.

We used Transcranial Magnetic Stimulation (TMS) to assess whether reading literal, non-literal (i.e., metaphorical, idiomatic) and fictive motion sentences modulates the activity of the motor system. Sentences were divided into three segments visually presented one at a time: the noun phrase, the verb and the final part of the sentence. Single pulse-TMS was delivered at the end of the sentence over the leg motor area in the left hemisphere and motor evoked potentials (MEPs) were recorded from the right gastrocnemius and tibialis anterior muscles. MEPs were larger when participants were presented with literal, fictive and metaphorical motion sentences than with idiomatic motion or mental sentences. These results suggest that the excitability of the motor system is modulated by the motor component of the verb, which is preserved in fictive and metaphorical motion sentences.

Transcranial direct current stimulation over Broca's region improves phonemic and semantic fluency in healthy individuals.

Previous studies have demonstrated that transcranial direct current stimulation (tDCS) can be proficiently used to modulate attentional and cognitive functions. For instance, in the language domain there is evidence that tDCS can fasten picture naming in both healthy individuals and aphasic patients, or improve grammar learning. In this study, we investigated whether tDCS can be used to increase healthy subjects' performance in phonemic and semantic fluency tasks, that are typically used in clinical assessment of language. Ten healthy individuals performed a semantic and a phonemic fluency task following anodal tDCS applied over Broca's region. Each participant underwent a real and a sham tDCS session. Participants were found to produce more words following real anodal tDCS both in the phonemic and in the semantic fluency. Control experiments ascertained that this finding did not depend upon unspecific effects of tDCS over levels of general arousal or attention or upon participants' expectations. These data confirm the efficacy of tDCS in transiently improving language functions by showing that anodal stimulation of Broca's region can enhance verbal fluency. Implications of these results for the treatment of language functions in aphasia are considered.

Transcranial magnetic stimulation of medial prefrontal cortex modulates face expressions processing in a priming task.

The medial prefrontal cortex (mPFC) and the right somatosensory cortex (rSC) are known to be involved in emotion processing and face expression recognition, although the possibility of segregated circuits for specific emotions in these regions remains unclear. To investigate this issue, we used transcranial magnetic stimulation (TMS) together with a priming paradigm to modulate the activation state of the mPFC and the rSC during emotional expressions discrimination. This novel paradigm allows analyzing how TMS interacts with the ongoing activity of different neuronal populations following prime processing. Participants were asked to discriminate between angry and happy faces that were preceded by a congruent prime (a word expressing the same emotion), an incongruent prime (a word expressing the opposite emotion) or a neutral prime. In TMS trials, a single pulse was delivered over the mPFC, rSC or Vertex (control site) between prime and target presentation. TMS applied over the mPFC significantly affected the priming effect, by selectively increasing response latencies in congruent trials. This indicates that the mPFC contains different neural representations for angry and happy expressions. TMS over rSC did not significantly affect the priming effect, suggesting that rSC is not involved in processing verbal emotional stimuli.

Present day's standards in microsurgery of low-grade gliomas.

Low-grade gliomas are slow growing intrinsic lesions that induces a progressive functional reshaping of the brain. Surgical removal of these lesions requires the combined efforts of a multidiscipinary team of neurosurgeon, neuroradiologist, neuropsychologist, neurophysiologist, and neurooncologists that all together contribute in the definition of the location, extension, and extent of functional involvement that a specific lesion has induced in a particular patient. Each tumor has induced particular and specific changes of the functional network, that varies among patients. This requires that each treatment plan should be tailored to the tumor and to the patient. When this is reached, surgery should be accomplished according to functional and anatomical boundaries, and has to aim to the maximal resection with the maximal patient functional preservation. This can be reached at the time of the initial surgery, depending on the functional organization of the brain, or may require additional surgeries, eventually intermingled with adjuvant treatments. The use of so called brain mapping techniques extend surgical indications, improve extent of resection with greater oncological impact, minimization of morbidity and increase in quality of life. To achieve the goal of a satisfactory tumor resection associated with the full preservation of the patients abilities, a series of neuropsychological, neurophysiological, neuroradiological and intraoperative investigations have to be performed. In this chapter, we will describe the rationale, the indications and the modality for performing a safe and rewarding surgical removal of low-grade gliomas by using these techniques, as well as the functional and oncological results.

The time course of idiom processing.

Recent neuropsychological and neurophysiological studies have suggested that the neural correlates of idiom processing are predominantly located in the left Brodmann's area (BA) 22 and, to some extent, in the prefrontal cortex. The present study explores the temporal dynamics of left prefrontal and temporal cortex in idiom processing by using repetitive transcranial magnetic stimulation (rTMS) in normal subjects. Forty-five opaque highly familiar idioms and 45 literal sentences were used. Forty-three subjects completed 5 blocks of 18 trials (9 idioms, 9 literal sentences) corresponding to 4 stimulation conditions (left prefrontal, left temporal, vertex, no-stimulation baseline). Each subject was assigned to one of three groups, which differed in the timing of stimulation delivery. A selective impairment in accuracy for idioms was found when rTMS was applied to the prefrontal and temporal cortex 80ms after picture presentation, confirming the role of these regions in this task. Moreover, rTMS to the prefrontal cortex, but not to the temporal cortex, continued to affect the performance with idiomatic sentences at the later time of 120ms. The results seem to suggest that the prefrontal region is involved in both the retrieval of the figurative meaning from semantic memory and the monitoring of the response by inhibiting alternative interpretations when a picture-matching task is used.

Testing idiom comprehension in aphasic patients: the effects of task and idiom type.

Idiom comprehension in 15 aphasic patients was assessed with three tasks: a sentence-to-picture matching task, a sentence-to-word matching task and an oral definition task. The results of all three tasks showed that the idiom comprehension in aphasic patients was impaired compared to that of the control group, and was significantly affected by the type of task and type of idiom. Whilst performance on the oral definition and sentence-to-picture matching tasks was similarly impaired, the patients performed significantly better on the sentence-to-word matching task. The results confirm the relevance of task and idiom type in drawing conclusions about figurative language interpretation in brain-damaged patients.

The neural correlates of phonological short-term memory: a repetitive transcranial magnetic stimulation study.

Neuropsychological reports and activation studies by means of positron emission tomography and functional magnetic resonance imaging have suggested that the neural correlates of phonological short-term memory are located in the left hemisphere, with Brodmann's area (BA) 40 being responsible for short-term storage, and BA 44 for articulatory rehearsal. However, a careful review of the literature on the role of left BA 40 shows that the data are equivocal. We tested these hypotheses by means of repetitive transcranial magnetic stimulation (rTMS). Participants performed four tasks: two phonological judgements, thought to require only articulatory rehearsal without the contribution of short-term storage; a digit span, which involves both, short-term storage and articulatory rehearsal; and a pattern span, this last being the control task. The sites of stimulation were left BA 40, left BA 44 and the electrode location v(tx), plus a baseline without TMS. Reaction times increased and accuracy decreased in the case of the phonological judgements and digit span after stimulation of both left sites, suggesting that BA 40, in addition to BA 44, is involved in phonological judgements. Possible explanations are discussed, namely, the possibility that (i) the neural correlates of rehearsal are not limited to BA 44 and (ii) phonological judgements involve processes other than rehearsal. We also consider the effects of using different tasks and responses to resolve some of the discrepancies in the literature.

Memory and executive functions in aneurysms of the anterior communicating artery.

The cognitive outcome of three groups of patients, who had undergone surgery for repair of a single ruptured intracranial aneurysm, was evaluated. We assessed performance on tests of executive functions and memory in a group of 15 patients tested at least 3 months after an aneurysm of the anterior communicating artery (ACoA) and in a group of 12 patients tested in the first month after the same pathology. Acute patients were more impaired overall than chronic ones, but the two groups significantly differed on two executive and one memory test. The performance of the ACoA patients was also compared to the performance of a group of 10 patients who had undergone surgery for an aneurysm located on the posterior communicating artery (PCoA) at least 3 months before the examination. Chronic ACoA and PCoA patients significantly differed in two memory and in two executive tests performance, with posterior patients being more impaired than anterior. An unexpected finding was the impairment of semantic memory in ACoA patients.

Famous face recognition and naming test: a normative study.

Tests of famous face recognition and naming, and tasks assessing semantic knowledge about famous people after presentation either of their faces or their names are often used in the neuropsychological examination of aphasic, amnesic and demented patients. A total of 187 normal subjects took part in this study. The aim was to collect normative data for a newly devised test including five subtests: famous face naming, fame judgement after face presentation and after name presentation, semantic knowledge about famous people after face presentation and after name presentation. Norms were calculated taking into account demographic variables such as age, sex and education and adjusted scores were used to determine inferential cut-off scores and to compute equivalent scores. Multiple regression analyses showed that age and education influenced significantly the performance on most subtests, but sex had no effect on any of them. Scores of the subtest evaluating fame judgements after name presentation were significantly influenced only by education. The only subtest whose scores were not influenced by any demographic variable was fame judgement after face presentation.

Understanding metaphors and idioms: a single-case neuropsychological study in a person with Down syndrome.

The ability of subject F.F., diagnosed with Down syndrome, to appreciate nonliteral (interpreting metaphors and idioms) and literal (vocabulary knowledge, including highly specific and unusual items) aspects of language was investigated. F.F. was impaired in understanding both metaphors and idioms, while her phonological, syntactic and lexical-semantic skills were largely preserved. By contrast, some aspects of F.F.'s executive functions and many visuospatial abilities were defective. The suggestion is made that the interpretation of metaphors and idioms is largely independent of that of literal language, preserved in F.F., and that some executive aspects of working memory and visuospatial and imagery processes may play a role.

Comprehension of metaphors and idioms in patients with Alzheimer's disease: a longitudinal study.

Language in patients with Alzheimer's disease has been extensively studied, with the exception of non-literal language comprehension. However, in our speech, we often make use of expressions, which are not necessarily interpreted on a literal ground. Comprehension of metaphors and idioms was examined in 39 patients with probable early Alzheimer's disease. The results showed that the decline of figurative language is not an early symptom of dementia and can occur independently from the impairment of propositional language. It was also found that metaphors and idioms differ as far as the predominant kind of error is concerned.

Slowly progressive aphasia: a four-year follow-up study.

This paper reports the long-term follow-up of GC, a patient with primary progressive aphasia of the fluent type. GC presented at onset with an anomia characterized by sparing of first letter knowledge, that applied mainly to proper names and living categories. No semantic deficits were observed in the first stage of the disease, and MRI showed a left temporal lobe atrophy with a gradient from the pole to the posterior regions, the latter being less involved. We now report the clinical evolution of GC from the 2nd to the 4th year of disease. As the disease progressed, the anomia became more severe and the phenomenon of first letter sparing was no longer detectable. Also semantic knowledge was gradually affected and, eventually, was dramatically lost. However, no other cognitive deficits were seen at the last examination. By that time, the temporal atrophy shown by MRI was bilateral, although still more evident on the left side.

The selective impairment of phonological processing in speech production.

We report the naming performance of a patient (DM) with a fluent progressive aphasia who made phonological errors in all language production tasks. The pattern of errors in naming was strikingly clear: DM made very many phonological errors that resulted almost always in nonword responses. The complete absence of semantic errors and the very low ratio of formal errors relative to nonword errors (1.6:30.3) in DM's performance are discussed in the context of recent claims about the nature of naming deficits in fluent aphasics. We argue that DM's performance makes highly improbable the claim that fluent aphasia results from global lesions affecting all levels of the lexical access system equally.

Upper and lower face apraxia: role of the right hemisphere.

The aim of this study was to evaluate face apraxia in left- and right-hemisphere-damaged patients both in the acute and chronic stage of their disease. Two newly devised tests that assess movements of the upper and lower face districts were employed. On the whole, the proportion of left-hemisphere-damaged patients showing face apraxia were 46 and 68% for upper and lower face, respectively. A substantial proportion of right-hemisphere-damaged patients also showed face apraxia, i.e. 44% upper face and 38% lower face. Concomitant variables such as general severity, locus of lesion, language or visuo-spatial impairments, presence of neglect, interval from stroke, peculiarity of clusters of items or scoring procedures did not account for these results. These findings suggest that face apraxia in some patients may affect movements of the upper face district and that the right hemisphere plays a significant part in both upper and lower face praxis.