Facundo Manes

Classification of primary progressive aphasia and its variants

This article provides a classification of primary progressive aphasia (PPA) and its 3 main variants to improve the uniformity of case reporting and the reliability of research results. Criteria for the 3 variants of PPA—nonfluent/agrammatic, semantic, and logopenic—were developed by an international group of PPA investigators who convened on 3 occasions to operationalize earlier published clinical descriptions for PPA subtypes. Patients are first diagnosed with PPA and are then divided into clinical variants based on specific speech and language features characteristic of each subtype. Classification can then be further specified as “imaging-supported” if the expected pattern of atrophy is found and “with definite pathology” if pathologic or genetic data are available. The working recommendations are presented in lists of features, and suggested assessment tasks are also provided. These recommendations have been widely agreed upon by a large group of experts and should be used to ensure consistency of PPA classification in future studies. Future collaborations will collect prospective data to identify relationships between each of these syndromes and specific biomarkers for a more detailed understanding of clinicopathologic correlations.

Impaired recognition and experience of disgust following brain injury.

Huntingtons disease can particularly affect peoples recognition of disgust from facial expressions, and functional neuroimaging research has demonstrated that facial expressions of disgust consistently engage different brain areas (insula and putamen) than other facial expressions. However, it is not known whether these particular brain areas process only facial signals of disgust or disgust signals from multiple modalities. Here we describe evidence, from a patient with insula and putamen damage, for a neural system for recognizing social signals of disgust from multiple modalities.

The contributions of lesion laterality and lesion volume to decision-making impairment following frontal lobe damage

Lesions to prefrontal cortex (PFC) in humans can severely disrupt everyday decision-making, with concomitant effects on social and occupational functioning. Forty-six patients with unilateral lesions to prefrontal cortex and 21 healthy control subjects were administered three neuropsychological measures of decision-making: the Iowa Gambling Task, the Cambridge Gamble Task, and the Risk Task. Magnetic resonance imaging (MRI) scans were acquired from 40 patients, with region of interest (ROI) mapping of prefrontal subregions. The frontal patients showed only limited damage in medial and orbital prefrontal cortex, but greater damage in lateral prefrontal regions of interest. Patients with right frontal lesions preferred the risky decks on the Iowa Gambling Task, and differed significantly from left frontal and control subjects. Within the right frontal group, the preference for the risky decks was correlated with the total lesion volume and the volume of damage outside of the ventromedial prefrontal region. Right and left frontal groups did not differ significantly on the Cambridge Gamble Task or the Risk Task, and performance was not associated with lesion volume. The results indicate a laterality effect on the Iowa Gambling Task, and the contribution of prefrontal regions outside the ventromedial region to task performance. The Cambridge Gamble Task and Risk Task were less sensitive to the effects of unilateral frontal lobe lesions, and may be more selectively associated with ventral prefrontal damage.

A neuropsychological battery to detect specific executive and social cognitive impairments in early frontotemporal dementia

Traditional cognitive tests may not be sensitive for the early detection of executive and social cognitive impairments in the behavioural variant of frontotemporal dementia. The aim of this study was to detect specific executive and social cognitive deficits in patients with early behavioural variant frontotemporal dementia using a battery of tests previously shown to be sensitive to frontal lobe dysfunction. Behavioural variant frontotemporal dementia patients and paired controls were assessed with a complete standard neuropsychological battery evaluating attention, memory, visuospatial abilities, language and executive functions. All participants were then assessed with our Executive and Social Cognition Battery, which included Theory of Mind tests (Mind in the Eyes, Faux Pas), the Hotel Task, Multiple Errands Task-hospital version and the Iowa Gambling Task for complex decision-making. Patients were divided into two groups according to their Addenbrookes Cognitive Examination scores, a measure of general cognitive status. Low Addenbrookes Cognitive Examination patients differed from controls on most tasks of the standard battery and the Executive and Social Cognition Battery. While high Addenbrookes Cognitive Examination patients did not differ from controls on most traditional neuropsychological tests, significant differences were found between this high-functioning behavioural variant of frontotemporal dementia group and controls on most measures of our Executive and Social Cognition Battery. Our results suggest that the Executive and Social Cognition Battery used in this study is more sensitive in detecting executive and social cognitive impairment deficits in early behavioural variant of frontotemporal dementia than the classical cognitive measures.

Executive function and fluid intelligence after frontal lobe lesions.

Many tests of specific ‘executive functions’ show deficits after frontal lobe lesions. These deficits appear on a background of reduced fluid intelligence, best measured with tests of novel problem solving. For a range of specific executive tests, we ask how far frontal deficits can be explained by a general fluid intelligence loss. For some widely used tests, e.g. Wisconsin Card Sorting, we find that fluid intelligence entirely explains frontal deficits. When patients and controls are matched on fluid intelligence, no further frontal deficit remains. For these tasks too, deficits are unrelated to lesion location within the frontal lobe. A second group of tasks, including tests of both cognitive (e.g. Hotel, Proverbs) and social (Faux Pas) function, shows a different pattern. Deficits are not fully explained by fluid intelligence and the data suggest association with lesions in the right anterior frontal cortex. Understanding of frontal lobe deficits may be clarified by separating reduced fluid intelligence, important in most or all tasks, from other more specific impairments and their associated regions of damage.

Contextual social cognition and the behavioral variant of frontotemporal dementia

The significance of social situations is commonly context-embedded. Although the role of context has been extensively studied in basic sensory processing or simple stimulus-response settings, its relevance for social cognition is unknown. We propose the social context network model (SCNM), a fronto-insular-temporal network responsible for processing social contextual effects. The SCNM may 1) update the context and use it to make predictions, 2) coordinate internal and external milieus, and 3) consolidate context-target associative learning. We suggest the behavioral variant of frontotemporal dementia (bvFTD) as a specific disorder in which the reported deficits in social cognition (e.g., facial recognition, empathy, decision-making, figurative language, theory of mind) can be described as context impairments due to deficits in the SCNM. Disruption of orbitofrontal-amygdala circuit, as well as the frontal, temporal, and insular atrophy in bVFTD, suggests a relationship between context-sensitive social cognition and SCNM. In considering context as an intrinsic part of social cognition, we highlight the need for a situated cognition approach in social cognition research as opposed to an abstract, universal, and decontextualized approach. The assessment of context-dependent social cognition paradigms, the SCNM, and their possible application to neuropsychiatric disorders may provide new insight into bvFTD and other related frontal disorders.

Decision-making cognition in neurodegenerative diseases

A large proportion of human social neuroscience research has focused on the issue of decision-making. Impaired decision-making is a symptomatic feature of a number of neurodegenerative diseases, but the nature of these decision-making deficits depends on the particular disease. Thus, examining the qualitative differences in decision-making impairments associated with different neurodegenerative diseases could provide valuable information regarding the underlying neural basis of decision-making. Nevertheless, few comparative reports of decision-making across patient groups exist. In this Review, we examine the neuroanatomical substrates of decision-making in relation to the neuropathological changes that occur in Alzheimer disease, frontotemporal dementia, Parkinson disease and Huntington disease. We then examine the main findings from studies of decision-making in these neurodegenerative diseases. Finally, we suggest a number of recommendations that future studies could adopt to aid our understanding of decision-making cognition.

Clinical effects of insular damage in humans.

Multiple disturbances following lesions of the insula are reviewed in the present article, including those related to autonomic function; gustatory, olfactory, auditory, somatosensory, and multimodal perception, as well as body awareness; the emotion of disgust; mood and willed action, addiction behavior, and language. Given the multiple and varied nature of the impairments revealed by lesion studies, we suggest that the insula, as a multimodal area, has a major role as a convergence zone implicated in the coordination between internal and external information through emotional subjective awareness. Methodological issues are discussed with attention paid to lesion etiology, and lesions involving adjacent areas to the insular cortex.

Taking both sides: do unilateral anterior temporal lobe lesions disrupt semantic memory?

The most selective disorder of central conceptual knowledge arises in semantic dementia, a degenerative condition associated with bilateral atrophy of the inferior and polar regions of the temporal lobes. Likewise, semantic impairment in both herpes simplex virus encephalitis and Alzheimers disease is typically associated with bilateral, anterior temporal pathology. These findings suggest that conceptual representations are supported via an interconnected, bilateral, anterior temporal network and that it may take damage to both sides to produce an unequivocal deficit of central semantic memory. We tested and supported this hypothesis by investigating a case series of 20 patients with unilateral temporal damage (following vascular accident or resection for tumour or epilepsy), utilizing a test battery that is sensitive to semantic impairment in semantic dementia. Only 1/20 of the cases, with a unilateral left lesion, exhibited even a mild impairment on the receptive semantic measures. On the expressive semantic tests of naming and fluency, average performance was worse in the left- than right-unilateral cases, but even in this domain, only one left-lesion case had scores consistently more than two standard deviations below control means. These results fit with recent parallel explorations of semantic function using repetitive transcranial magnetic stimulation as well as functional imaging in stroke aphasic and neurologically intact participants. The evidence suggests that both left and right anterior temporal lobe regions contribute to the representation of semantic memory and together may form a relatively damage-resistant, robust system for this critical aspect of higher cognition.

Improved executive functioning following repetitive transcranial magnetic stimulation.

Abstract—The cognitive effects of active and sham repetitive transcranial magnetic stimulation (rTMS) were examined in 19 middle-aged and elderly patients with refractory depression. Patients received either active (n = 9) or sham (n = 10) rTMS targeted at the anterior portion of the left middle frontal gyrus. Patients in the active rTMS group improved significantly on a test of cognitive flexibility and conceptual tracking (Trail Making Test–B).