Guido Gainotti

• Emeritus Professor of Neurology
• Università Cattolica del Sacro Cuore

Background: In this narrative review, we have surveyed results obtained from a research program dealing with the role of semantic memory disorders as a predictor of progression from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). Objectives: In this research program, we have taken into account many different putative markers, provided...

Taking into the account both the severity and the consistency of performances obtained on memory tests by patients with amnestic mild cognitive impairment (aMCI) could improve the power to predict their progression to Alzheimer’s disease. For this purpose, we constructed the Episodic Memory Score (EMS), which is obtained by subdividing in tertiles...

A recent meta-analysis of functional neuroimaging contrasts between emotional and neutral face processing has shown that the processing of facial emotions can be better classified according to threat detection than emotional valence, with the authors suggesting that their data are inconsistent with both the right-hemisphere and valence models of em...

In this paper I discuss the main models that have tried to explain brain asymmetries for emotions. The first models, based on clinical observations, proposed either a general right hemisphere dominance for emotions (the’right hemisphere’) model or a different specialization of the right hemisphere for negative and of the left hemisphere for positiv...

The many stimulating contributions to this Special Issue of Brain Science focused on some basic issues of particular interest in current research, with emphasis on human recognition using faces, voices, and names [...]

Several studies have shown that emotions are asymmetrically represented in the human brain and have proposed three main models (the ‘right hemisphere hypothesis’, the ‘approach-withdrawal hypothesis’ and the ‘valence hypothesis’) that give different accounts of this emotional laterality. Furthermore, in recent years, many investigations have sugges...

This review aimed to evaluate whether the association between ‘anosognosia for hemiplegia’ and lesions of the right hemisphere points to a special self-awareness role of the right side of the brain, or could instead be due to a working mode typical of the right hemisphere. This latter viewpoint is consistent with a recently proposed model of human...

In his target article, Morin claims that ideographic codes are exceedingly difficult to use. In my commentary I will show that the use of Bliss symbols does not improve the communicative abilities of aphasic patients with severe language disorders. This failure to remediate communication disorders may result from disruption of inner language allowi...

The aim of this study was to shed light on the neural substrate of conceptual representations starting from the construct of higher-order convergence zones and trying to evaluate the unitary or non-unitary nature of this construct. We used the ‘Thematic and Taxonomic Semantic (TTS) task’ to investigate (a) the neural substrate of stimuli belonging...

Semantic Variant of Primary Progressive Aphasia (svPPA) has often been considered as a loss of knowledge stored in semantic memory, but might also be due to a general disruption of mechanisms allowing the acquisition, storage, and retrieval of semantic memories. In order to assess any parallelism in svPPA patients between loss of semantic knowledge...

Purpose of Review Pronagnosia is a rare acquired or developmental pathological condition that consists of a selective difficulty to recognize familiar people by their voices. It can be distinguished into two different categories: apperceptive phonagnosia, which denotes a purely perceptual form of voice recognition disorder; and associative phonagno...

Background: Experimental investigations and clinical observations have shown that not only faces but also voices are predominantly processed by the right hemisphere. Moreover, right brain-damaged patients show more difficulties with voice than with face recognition. Finally, healthy subjects undergoing right temporal anodal stimulation improve the...

The first minor aim of this synthetical historical survey consisted in showing that the discovery of the internal organization of language within the left hemisphere has been mainly determined by theoretical models and cultural factors, whereas the discovery of the left lateralisation of language and of the right lateralization of emotions and of o...

We administered to large groups of patients with neoplastic or degenerative damage affecting the right or left ATL, the 'Famous People Recognition Battery' (FPRB), in which subjects are required to recognize the same 40 famous people through their faces, voices and names, to clarify which components of famous people recognition are lateralized. At...

A systematic review of investigations evaluating hemispheric asymmetries for emotions in primates was undertaken to individuate the most consistent lines of research allowing to check the hypothesis of a continuum in emotional lateralization across vertebrates. We reviewed studies on the lateralization of emotional expression (N=31) and perception...

This review evaluated if the hypothesis of a causal link between the left lateralization of language and other brain asymmetries could be supported by a careful review of data gathered in patients with unilateral brain lesions. In a short introduction a distinction was made between brain activities that could: (a) benefit from the shaping influence...

The hypothesis assuming that the right hemisphere may play a critical role in emotional processing was raised by clinical data which showed that patients with right brain lesions often show abnormal patterns of emotional behavior [...]

Since the description of anosognosia for hemiplegia by Babinski (who also stressed the links between anosognosia and right hemisphere damage) both motivational and cognitive mechanisms have been advanced to explain this awareness disorder. In this review I will discuss first the neurophysiological mechanisms that can impede the discovery of the mot...

Even if for many years hemispheric asymmetries have been considered as a uniquely human feature, an increasing number of studies have described hemispheric asymmetries for various behavioral functions in several nonhuman species. An aspect of animal lateralization that has attracted particular attention has concerned the hemispheric asymmetries for...

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...

Eyelid closing or opening disorders have been only sporadically described in patients with focal brain lesions over the last decades. Furthermore, the restricted number of reports and the lack of uniform clinical assessment of affected individuals did not allow to define more in depth the clinical features and the underlying neural correlates of th...

Background The assessment of semantic memory may be a useful marker to identify individuals with mild cognitive impairment (MCI) who will progress to Alzheimer’s disease (AD) in the early stages of the disease. Objective The aim of this five-year follow-up longitudinal study is to assess whether semantic assessment could predict progression in MCI...

Many influential authors maintain that, even if emotions are conscious experiences, the processing of information that produces emotions is usually unconscious. This chapter discusses the nonconscious aspects of emotional processing and the critical role played in them by the right hemisphere. This chapter first reviews the studies that have demons...

Objective Mild cognitive impairment is the main risk factor of dementia. Previous evidence has claimed that subjects with memory disturbances associated with impairment of other cognitive domains (multiple domain amnesic MCI) are at the highest risk of developing dementia. To date, a shared definition of amnesic MCI multiple domain (aMCI-MD) is sti...

Acquired prosopagnosia is usually a consequence of bilateral or right hemisphere lesions and is often associated with topographical disorientation and dyschromatopsia. Left temporo-occipital lesions sometimes result in a face recognition disorder but in a context of visual object agnosia with spared familiarity feelings for faces, usually in left-h...

The aim of the present rewiew consists of surveying the role that non-verbal tasks based on gestures and free drawing can have on the assessment of defective representational activities and on the rehabilitation of aphasic patients. The relationships between verbal and non-verbal cognitive disorders of aphasic patients and the underlying mechanisms...

According to the original “hub-and-spoke” model of conceptual representations, the neural network for semantic memory requires a single convergence zone located in the anterior temporal lobes (ATLs). However, a more recent version of this model acknowledges that a graded specialization of the left and right ATLs might emerge as a consequence of the...

Disagreement exists regarding representational and connectionist interpretations of semantic knowledge subserved by the right versus left anterior temporal lobes (ATLs). These interpretations predict a different pattern of impairment in patients with a right unilateral ATL lesion. We conducted a neuropsychological study of a selective semantic pict...

Objectives Within the large topic of naming disorders, an important and separated chapter belongs to proper names. Defects of proper naming could be a selective linguistic problem. Sometimes, it includes names belonging to various kinds of semantically unique entities, but other times, it has been observed for famous people proper names only. Accor...

This chapter concerns some recent trends in the study of the links between emotions and brain laterality and separately discusses: (a) negative data obtained by functional neuroimaging studies of the neural correlates of emotions; (b) laterality effects in brain structures that have a crucial role in specific emotional functions; (c) emotional and...

The existence of priviledged relations betweeen the emotional system and sympathetic activities is suggested by the fact that basic emotions are conceived as an emergency system, and that the aim of sympathetic activities is to allow a strong and quick response to emergency situations. Furthermore, both basic emotions and the sympathetic system are...

In this chapter, two general neurobiological models recently advanced by Gainotti and by Craig to explain most clinical, neuropsychological and neurobiological data reported in previous chapters of this volume will be taken into account. Gainotti’s model develops the ‘right hemisphere hypothesis’ and assumes that the main features of the emotional...

This chapter will take into account some psychopathological implications of hemispheric asymmetries for emotions that are consistent respectively with the ‘valence hypothesis’ and the ‘right hemisphere hypothesis’. The former predicts that major post-stroke depression and secondary mania are caused respectively by left and right hemispheric lesions...

This chapter will take into account the brain structures which play a critical role in different components and hierarchical levels of emotions. Concerning the neural substrates of different components of emotions, a distinction will be made among structures that (a) underlie the evaluation of emotional significance, (b) are involved in the generat...

In this chapter, an attempt will be made to define the word ‘emotions’ by stressing the adaptive value of the behavioural schemata that are usually included under this term and the difficulty of distinguishing emotions from other behavioural patterns belonging to different but contiguous areas. Similarities and differences between the two adaptive...

In this chapter the history of research on emotional laterality will be taken into account, starting from the pioneering investigations in this area and from the first observations of the different emotional behaviour shown by right and left brain-damaged patients. The experimental and clinical investigations which have studied the nonverbal commun...

This book focuses on asymmetries in brain structure and their role in emotional functions (such as amygdala in emotional comprehension, the ventro-medial prefrontal cortex in the integration between cognition and emotion and in the control of emotional reactions, and the anterior insula in the experience of emotions). The idea of hemispheric asymme...

Categorical verbal fluency tests (CFT) are commonly used to assess the integrity of semantic memory in individuals with brain damage. Persons with Dementia of the Alzheimer’s Type display a reduced output on CFT, and a similar pattern has been reported in persons with amnesic Mild Cognitive Impairment (aMCI). The aims of the present study were to a...

The present commentary revisits some old data, concerning the same kind of visual avoidance behaviors described by Otero and Levenson's (2019) in their target paper and proposes a new perspective on the neural underpinnings of such behaviors. A lack of visual avoidance in response to a shocking film clip had been unexpectedly observed during a stud...

Even if Babinski (1914) is usually considered as the discoverer of anosognosia, other authors before him contributed to the development of this construct. Von Monakow (1885) and Dejerine and Vialet (1893) gave the first descriptions of patients with cortical blindness who were unaware of their disability, but did not distinguish this unawareness fr...

Introduction: Both the neuropsychological study of patients with category-specific semantic disorders (CSSD) and the experimental research on categorical processing in healthy subjects (HSs) have shown that men are mainly impaired with fruits and vegetables and women with animals and artifacts. Since this difference is more striking in patients wit...

Background: Two main models have been advanced to explain the asymmetries observed in the representation and processing of emotions. The first model, labeled “the right hemisphere hypothesis,” assumes a general dominance of the right hemisphere for all emotions, regardless of affective valence. The second model, named “the valence hypothesis,” assu...

The target article carefully describes the memory system, centered on the temporal lobe that builds specific memory traces. It does not, however, mention the laterality effects that exist within this system. This commentary briefly surveys evidence showing that clear asymmetries exist within the temporal lobe structures subserving the core system a...

Different models of emotional lateralization, advanced since the first clinical observations raised this issue, will be reviewed following their historical progression. The clinical investigations that have suggested a general dominance of the right hemisphere for all kinds of emotions and the experimental studies that have proposed a different hem...

Earlier studies, which suggested that anosognosia of hemiplegia might be related to right hemisphere (RH) lesions did not control for the influence of confounding variables, such as aphasia, in patients with left-hemisphere lesions and unilateral neglect in those with RH lesions. These confounding variables are absent in patients with degenerative...

Objective: Familiar face recognition disorders are often observed in patients with lesions of the right anterior temporal lobe (ATL). It is not clear, however, if this defect must be considered as a form of associative prosopagnosia, or as a multimodal (face and voice) people recognition disorder, because voice recognition is rarely examined in the...

Models advanced to explain hemispheric asymmetries in representation of emotions will be discussed following their historical progression. First, the clinical observations that have suggested a general dominance of the right hemisphere for all kinds of emotions will be reviewed. Then the experimental investigations that have led to proposal of a di...

A very challenging problem in the domain of the cognitive neurosciences is to explain why herpes simplex encephalitis and semantic dementia show, respectively, a category-specific semantic disorder for biological entities and an across-categories semantic disruption, despite highly overlapping areas of anterior temporal lobe damage. The aim of the...

Introduction: Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Conse...

In this normative study, we investigated famous people recognition through personal name, using as stimuli the names of the same 40 Italian famous persons whose faces and voices had been utilized for the normative study of the Famous People Recognition Battery. For each famous people, we assessed name familiarity, person identification (when the na...

Since the classic papers of Kleist, Mayer Gross, and Critchley, constructional apraxia (CA) has been considered to be a typical sign of a parietal lobe lesion, and as a precious tool to appreciate the spatial abilities subserved by this lobe. However, the development of more sophisticated neuropsychologic models and methods of investigation has rev...

Visual neglect is a disabling consequence of right hemisphere damage, whereby patients fail to detect left-sided objects. Its precise mechanisms are debated, but there is some consensus that distinct component deficits may variously associate and interact in different patients. Here we used a touch-screen based procedure to study two putative compo...

The present study aimed at assessing if the ability to predict progression from amnesic Mild Cognitive Impairment (aMCI) to dementia is improved by considering the presence at the baseline of Single Photon Emission Computed Tomography (SPECT) perfusion abnormalities in addition to a defect of long term memory. The Episodic Memory Score (EMS), a glo...

Poor disease awareness ('anosognosia') is often observed in patients with various disabilities caused by brain damage. The lack of disease awareness can be due to the disruption of specific cognitive mechanisms and the development of psychodynamic mechanisms of denial. The aim of this paper is to review how these phenomena were discovered and evolv...

Changes in health care and disease epidemiology have shifted the attention of neuropsychologists and cognitive neuroscientists from vascular lesions to degenerative diseases or other bilateral brain lesions. This displacement of attention from vascular patients to patients with degenerative brain diseases allowed the discovery of hitherto unexplore...

Controversies exist over the format of person-specific semantic representations in healthy subjects and the loss of part of these representations in conditions of brain pathology. Some authors have suggested that in brain-damaged patients item-specific consistency of errors through different recognition modalities might indicate a loss of person-sp...

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...

This paper reviews some controversies concerning the original and revised versions of the 'hub-and-spoke' model of conceptual representations and their implication for abstraction capacity levels. The 'hub-and-spoke' model, which is based on data gathered in patients with semantic dementia (SD), is the most authoritative model of conceptual knowled...

In semantic tasks, sex-related categorical differences, in the form of better processing of fruits and vegetables by women and of artifacts (human-made objects) and animals by men, have been reported both in healthy participants and in brain-damaged patients. Researchers' interpretation of these sex-related categorical asymmetries has, however, bee...

We report the case of a 48 year old men who developed a selective impairment in famous voice recognition after ischemic stroke in right subcortical structures (lenticular nucleus and head of the caudate) and right anterior temporal lobe. He underwent fibrinolytic treatment. During the following days he progressively recovered and was discharged wit...

Background: Famous face and voice recognition is reported to be impaired both in semantic dementia (SD) and in Alzheimer's Disease (AD), although more severely in the former. In AD a coexistence of perceptual impairment in face and voice processing has also been reported and this could contribute to the altered performance in complex semantic task...

This handbook is currently in development, with individual articles publishing online in advance of print publication. At this time, we cannot add information about unpublished articles in this handbook, however the table of contents will continue to grow as additional articles pass through the review process and are added to the site. Please note...

It is well established that certain categories of objects are processed more efficiently than others in specific tasks; a phenomenon known as category-specificity in perceptual and conceptual processing. In the last two decades there have also been several reports of gender differences in category-specificity. In the present experiments we test the...

Objective Semantic verbal fluency (SVF) tests are widely used in clinical neuropsychology. We propose the standardization and clinical validation of a new SVF test based on the production of names of birds and articles of furniture (Birds and Articles of Furniture test—BAF). Methods A sample of 268 subjects aged 40 years or more underwent the test...

Drawing is a multicomponential process that can be impaired by many kinds of brain lesions. Drawing disorders are very common in Alzheimer’s disease and other forms of dementia, and can provide clinical information for the distinction of the different dementing diseases. In our review we started from an overview of the neural and cognitive bases of...

The models advanced to explain right hemisphere (RH) language function can be divided into two main types. According to the older (lower-level) models, RH language reflects the ontogenesis of conceptual and semantic-lexical development; the more recent models, on the other hand, suggest that the RH plays an important role in the use of higher-level...

In this prospective longitudinal study, conducted in a large sample of amnestic MCI patients over a three-year period, we investigated the recently advanced proposal that unadjusted test scores obtained at baseline on long-term memory tests are more reliable than age- and education-corrected scores in predicting progression from aMCI to AD. Our exp...

Background and purpose: Depression is common amongst subjects with multiple sclerosis (MS), and several investigations have explored different determinants of this condition, including physical disability, psychological and psychosocial factors. The brain derived neurotrophic factor (BDNF) Val66Met polymorphism has been associated with depression....

A Comparison between Anxious-Depressive Disorders of Stroke and Multiple Sclerosis Patients, Evaluated with Specific Twin Scales Objective: High levels of depression and anxiety are usually observed in patients with stroke and multiple sclerosis. Many studies have been conducted to clarify the factors subsuming these disorders, but all these invest...

The domain of emotions corresponds to the consciousness model proposed by Morsella et al. The action schemata unconsciously activated by spontaneous emotions are indeed automatically selected from a small number of innate operative patterns, whereas behavioral responses selected at the cognitive level of emotional processing consist of strategic pl...

Several anatomo-clinical investigations have shown that familiar face recognition disorders not due to high level perceptual defects are often observed in patients with lesions of the right anterior temporal lobe (ATL). The meaning of these findings is, however, controversial, because some authors claim that these patients show pure instances of mo...

The aims of the present experiment was to investigate: (a) if transient disruption of neural activity in the right (RTP) or left temporal pole (LTP) can interfere with the development of a familiarity feeling to the presentation of faces/written names of famous/unknown people; and (b) if this interference specifically affects the familiarity for fa...

The aim of the present survey was to review clinical and experimental data concerning the visual (face), auditory (voice) and verbal (name) channels through which familiar people are recognized, by contrasting these data with assumptions made by modular cognitive models of familiar people recognition. Particular attention was paid to the fact that...

The models advanced to explain right hemisphere (RH) language function can be divided into two main types. According to the older (lower-level) models, RH language reflects the ontogenesis of conceptual and semantic-lexical development; the more recent models, on the other hand, suggest that the RH plays an important role in the use of higher-level...

Background: The role of the right hemisphere (RH) in the recovery of language is quite controversial. Aims: The aim of the present survey consisted in taking into account three main models advanced to explain the reconstitution of language systems: (1) the "perilesional hypothesis," which maintains that language recovery is mainly subsumed by left...

The present review aimed to check two proposals alternative to the original version of the 'semantic hub' hypothesis, based on Semantic Dementia (SD) data, which assumed that left and right anterior temporal lobes (ATLs) store in a unitary, amodal format all kinds of semantic representations. The first alternative proposal is that the right ATL mig...

The present review aims to summarize the debate in contemporary neuroscience between inborn and experience-dependent models of conceptual representations that goes back to the description of category-specific semantic disorders for biological and artifact categories. Experience-dependent models suggest that categorical disorders are the by-product...

An important debate exists in contemporary cognitive neuroscience about the innate or experience-dependent origin of the brain representation of conceptual categories. The 'domains of knowledge' hypothesis maintains that innate factors subsume the categorical organization at the brain level of animals, plant life and artefacts. On the other hand, t...

Aims: To investigate the relationship between psychotic symptoms and cognitive impairment in Alzheimer's disease (AD). Methods: A total of 108 subjects affected by AD were subdivided into subjects without delusions (ND), subjects with paranoid delusions (PD), subjects with delusional misidentifications (DM), subjects with both DM and PD (DM+PD),...

Since the early 1960s, human neuropsychology, the study of brain-behavior interrelations, mainly based on the analysis of their pathological variations, brought about by brain damage, has had a remarkable systematical development in Italy. All this started in Milan, with the neurologist Ennio de Renzi, and his collaborators (Luigi Vignolo, then Ann...

Semantic and, to a lesser extent, phonological verbal fluency tasks are impaired in Alzheimer's disease (AD) and in amnesic mild cognitive impairment (aMCI). Furthermore, both fluency tasks have been considered as possible markers of conversion from aMCI to AD. Up to recent years, the use of fluency tasks has been limited to word count, but, more r...

Prosopagnosia has been considered for a long period of time as the most important and almost exclusive disorder in the recognition of familiar people. In recent years, however, this conviction has been undermined by the description of patients showing a concomitant defect in the recognition of familiar faces and voices as a consequence of lesions e...

From the first research on aphasia, it has been shown that, in addition to verbal communication disorders, aphasic patients often have difficulty on non-verbal cognitive tasks, which can actually be solved without the use of language. In this survey, I will discuss in a historical perspective the different interpretations provided by classical and...

Subjects with Mild Cognitive Impairment (MCI) are normally classified according to the presence of episodic memory deficits associated or not to disturbances of other cognitive domains. The present study had two aims: to identify discrete subtypes of amnestic MCI (a-MCI) with hippocampal atrophy; and to assess if the identified subtypes show differ...

The present survey develops a previous position paper, in which I suggested that the multimodal semantic impairment observed in advanced stages of semantic dementia is due to the joint disruption of pictorial and verbal representations, subtended by the right and left anterior temporal lobes, rather than to the loss of a unitary, amodal semantic sy...

Since the classical Babinski’s (1914) observation of lack of awareness (“anosognosia”) for a left-sided hemiplegia, the problem of the mechanisms underlying this surprising phenomenon has been raised. Most authors have stressed the links between right hemisphere and emotional processes, considering anosognosia as an abnormal emotional reaction, cau...