Neural alterations underlying executive dysfunction in Parkinson's disease: A systematic review and coordinate-based meta-analysis of functional neuroimaging studies.

Parkinson's Disease's (PD) neuropsychological profile is often characterized by altered performance in executive functions (EF) tasks, with a remarkable impact on patients' quality of life. To date, the available neuroimaging literature lacks conclusive evidence about neural patterns underlying EF deficits in PD. Here, we aimed to synthesize the results of PET/fMRI studies examining the differences in brain activation between PD patients and controls during EF tasks, focusing on the three main EF sub-components: cognitive flexibility, working memory, and response inhibition. We conducted a coordinate-based meta-analysis to assess the converging alterations in brain activity in PD patients compared to controls. We assessed the association between aberrant patterns of activity and the EF sub-domains. We found a significant association between hypoactivation patterns in PD converging at the level of the right inferior frontal gyrus in response inhibition tasks, whereas hypoactivation in the left inferior frontal gyrus was found in association with the cognitive flexibility domain. Our results confirm the existence of neural alterations in PD patients in relation to specific EF sub-domains.

Back and front peripersonal space: behavioural and EMG evidence of top-down and bottom-up mechanisms.

Previous studies have identified a 'defensive graded field' in the peripersonal front space where potential threatening stimuli induce stronger blink responses, mainly modulated by top-down mechanisms, which include various factors, such as proximity to the body, stimulus valence, and social cues. However, very little is known about the mechanisms responsible for representation of the back space and the possible role of bottom-up information. By means of acoustic stimuli, we evaluated individuals' representation for front and back space in an ambiguous environment that offered some degree of uncertainty in terms of both distance (close vs. far) and front-back egocentric location of sound sources. We aimed to consider verbal responses about localization of sound sources and EMG data on blink reflex. Results suggested that stimulus distance evaluations were better explained by subjective front-back discrimination, rather than real position. Moreover, blink response data were also better explained by subjective front-back discrimination. Taken together, these findings suggest that the mechanisms that dictate blink response magnitude might also affect sound localization (possible bottom-up mechanism), probably interacting with top-down mechanisms that modulate stimuli location and distance. These findings are interpreted within the defensive peripersonal framework, suggesting a close relationship between bottom-up and top-down mechanisms on spatial representation.

The Semantic Association Test (SAT): normative data from healthy Italian participants and a validation study in aphasic patients.

The Semantic Association Test assesses several aspects of Semantic Memory (Categorical, Encyclopedic, Functional, and Visual Encyclopedic associations: CAs, EAs, FAs and VEAs), using a picture-to-picture matching paradigm. Normative data were collected from a group of 329 healthy participants (178 females) with mean 51.1 (range 20-90) years of age and mean 11.89 (range 5-19) years of education. Raw scores of healthy participants, pre-calculated correction factors for age and educational level, and Equivalent Scores are provided. The SAT was validated in a sample of 139 left brain-damaged persons with aphasia (PWA). Both groups (healthy participants and PWA) scored worse in the CA and EA conditions. The performance of the PWA group was overall defective, and global aphasics scored worse than persons with other types of aphasia. However, several PWA did not show impairments in the SAT. Dissociations were also found, with individual PWA showing defective performance confined to a single category. These results present the SAT as a tool that is useful to detect impairments of visual Semantic Memory, providing normative data from healthy participants and a validation study in PWA.

Explicit motor sequence learning after stroke: a neuropsychological study.

Motor learning interacts with and shapes experience-dependent cerebral plasticity. In stroke patients with paresis of the upper limb, motor recovery was proposed to reflect a process of re-learning the lost/impaired skill, which interacts with rehabilitation. However, to what extent stroke patients with hemiparesis may retain the ability of learning with their affected limb remains an unsolved issue, that was addressed by this study. Nineteen patients, with a cerebrovascular lesion affecting the right or the left hemisphere, underwent an explicit motor learning task (finger tapping task, FTT), which was performed with the paretic hand. Eighteen age-matched healthy participants served as controls. Motor performance was assessed during the learning phase (i.e., online learning), as well as immediately at the end of practice, and after 90 min and 24 h (i.e., retention). Results show that overall, as compared to the control group, stroke patients, regardless of the side (left/right) of the hemispheric lesion, do not show a reliable practice-dependent improvement; consequently, no retention could be detected in the long-term (after 90 min and 24 h). The motor learning impairment was associated with subcortical damage, predominantly affecting the basal ganglia; conversely, it was not associated with age, time elapsed from stroke, severity of upper-limb motor and sensory deficits, and the general neurological condition. This evidence expands our understanding regarding the potential of post-stroke motor recovery through motor practice, suggesting a potential key role of basal ganglia, not only in implicit motor learning as previously pointed out, but also in explicit finger tapping motor tasks.

Consecutive and temporally distant perseverations after right brain damage: A prospective study.

Objective: Right brain-damaged patients may show omissions and/or additional marks in target cancellation. The latter is classified as perseverative behavior and has been attributed to defective response inhibition or attentional disengagement deficit. This study aimed at (a) verifying that consecutive (immediate) and return (temporally distant) motor perseverations could be due to different mechanisms; (b) investigating the relationships among different types of perseveration (e.g., consecutive, return, scribble), spatial neglect and the impairment in specific components of executive functioning. Method: Seventeen right brain-damaged patients underwent letter, star, bell, and apple cancellation tasks. A global index for each type of perseveration found and Mean Position of Hits, as a neglect index, were calculated. The following components of executive functioning were evaluated: motor programming (Frontal Assessment Battery [FAB] subtest), inhibitory control FAB, interference sensitivity (FAB and Stroop color-word interference test), set-shifting (Weigl sorting test, Phonemic/semantic alternate fluencies), and working memory (Backward Digit span). Results: Ten patients out of 17 showed some degree of perseveration. Regularized linear regression analyses demonstrated that interference sensitivity and Stroop test performances were related to return perseverations and backward digit to scribble ones. No significant relationships were found for consecutive perseverations and between neglect and any type of perseverations. Conclusions: The present study showed that return perseverations might have a distinct etiology from consecutive ones, being related to an inability to update and shift between action programs according to the visual stimuli. A finer classification of perseverations could help in unveiling the neuropsychological mechanisms underlying each type of behavior. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The Focal Attention Window Size Explains Letter Substitution Errors in Reading.

Acquired Neglect Dyslexia is often associated with right-hemisphere brain damage and is mainly characterized by omissions and substitutions in reading single words. Martelli et al. proposed in 2011 that these two types of error are due to different mechanisms. Omissions should depend on neglect plus an oculomotor deficit, whilst substitutions on the difficulty with which the letters are perceptually segregated from each other (i.e., crowding phenomenon). In this study, we hypothesized that a deficit of focal attention could determine a pathological crowding effect, leading to imprecise letter identification and consequently substitution errors. In Experiment 1, three brain-damaged patients, suffering from peripheral dyslexia, mainly characterized by substitutions, underwent an assessment of error distribution in reading pseudowords and a T detection task as a function of cue size and timing, in order to measure focal attention. Each patient, when compared to a control group, showed a deficit in adjusting the attentional focus. In Experiment 2, a group of 17 right-brain-damaged patients were asked to perform the focal attention task and to read single words and pseudowords as a function of inter-letter spacing. The results allowed us to confirm a more general association between substitution-type reading errors and the performance in the focal attention task.

The downsized hand in personal neglect.

Introduction: Personal neglect (PN) refers to a form of hemi-inattention toward the contralesional body space and it usually occurs following a right brain lesion. Recent studies suggest that PN indicates a disorder of body representation. Specifically, patients with PN show difficulties in identifying differences between left and right hands and have an altered visuospatial body map, which is associated with disrupted mental body representations. However, the metric representation of the body, and in particular the hands, has not been systematically addressed in patients showing this form of neglect. Method: In the present study, we have investigated this representation by testing the perceived hands' width of 11 hemiplegic patients with right hemisphere cerebral lesions (5 with PN) and 12 healthy controls on a judgment of passability task. Patients and controls were asked to imagine inserting their hand (left and right) through a series of vertical apertures of different sizes and to judge whether their hand could fit through. Due to the heterogeneity of the data, both parametric and non-parametric approaches were used. Furthermore, additional single-case analyses were conducted. Results: Study findings showed that patients with PN showed a significant underestimation of the left hand compared with their right hand. In contrast, whilst the right hand was equally distorted in both patients' groups, the hemiplegic patients with no evidence of PN tended to perceive the affected hand as larger than their ipsilesional one. Conclusions: In line with the literature, our findings confirm an underlying distorted body representation following right brain damage. However, for the first time, we report both a quantitative and qualitative difference in impact of hemiplegia and PN on body representation of the contralesional body space.

Can the right hemisphere read? A behavioral and disconnectome study on implicit reading in a patient with pure alexia.

Patients with pure alexia have major difficulties in reading aloud. However, they often perform above chance level in reading tasks that do not require overt articulation of the target word - like lexical decision or semantic judgment - a phenomenon usually known as "implicit reading." There is no agreement in the literature on whether implicit reading should be attributed to relative sparing of some left hemisphere (LH) reading centers or rather to signs of compensatory endeavors by the right hemisphere (RH). We report the case of an 81-year-old patient (AA) with pure alexia due to a lesion involving the left occipital lobe and the temporal infero-mesial areas, as well as the posterior callosal pathways. Although AA's reading was severely impaired and proceeded letter by letter, she showed an above-chance-level performance for frequent concrete words in a tachistoscopic lexical decision task. A structural disconnectome analysis revealed that AA's lesion not only affected the left occipital cortex and the splenium: it also disconnected white-matter tracts meant to connect the visual word-form system to decision-related frontal areas within the LH. We suggest that the RH, rather than the LH, may be responsible for patient AA's implicit reading.

Correction to: The assessment of severe lexical disorders in Italian individuals with aphasia.

This article was published with incomplete Table 4. The Equivalent scores were missing during the submission. The correct Table is presented here.

The assessment of severe lexical disorders in Italian individuals with aphasia.

Tests and batteries used in the evaluation of language impairments are overly complex and often ineffective (too difficult) in the assessment of post-stroke patients affected by severe aphasia (global aphasia). The present study reports details on the construction and standardization of a new Italian battery of tasks, specifically designed to assess severe lexical disorders in acquired aphasia (Battery for the Assessment of Severe Acquired Lexical Damage in Italian, BASALDI). The battery is composed of a common set of 64 stimuli (concrete nouns), belonging to both living and non-living categories, and consists of four lexical tasks assessing picture naming, repetition, reading aloud, and oral comprehension. The item selection was based on word frequency, word length, and phonological-articulatory complexity, namely the presence of continuant vs. plosive phones, a variable that may interact with word production in case of severe language damage. Standardization (naming agreement) of a new set of 64 colored images and normative data on Italian healthy subjects pooled across homogenous subgroups for age, gender, and education are reported. Finally, for the four tasks, percentile ranks and z-scores were calculated from a pool of 92 left brain-damaged patients affected by aphasia of different types and severity. The battery allows a fine investigation of lexical disorders, being suitable for diagnostic assessment of mild-to-moderate and severe aphasic lexical deficits, detection of changes over time, and possible dissociations between tasks.

Setting the midpoint of sentences: The role of the left hemisphere.

The human brain has a remarkable capacity to focus processing resources based on the features and the relevance of the task at hand. The two cerebral hemispheres contribute differentially to this capacity, with the left hemisphere linguistic and right hemisphere visuo-spatial abilities each offering unique contributions. For example, previous research has established that healthy participants set the subjective mid-point of written sentences more leftwards of center, compared to unpronounceable letter strings or simple lines. Remarkably, patients with right hemisphere damage exhibiting unilateral spatial neglect also show this pattern, even though, as well known in the literature, they tend toward a rightward- bias for non-linguistic stimuli. This evidence suggests that the leftward bias for sentential material is due to linguistic, mainly left-hemisphere mediated processes, which are largely unimpaired in right brain-damaged patients, and intact in heathy participants. To test this hypothesis, we compared sentence bisection performance to that of letter strings and simple lines in left brain-damaged patients (with and without aphasia). If the larger leftward bias in the bisection of sentential material is based on linguistic processes, then the left brain-damaged patients should show a reduction or absence of a leftward bias in sentence bisection. We tested twenty-four left brain-damaged patients (12 with aphasia and 12 without aphasia), and 24 age-matched elderly participants (patients and controls were all right-handed). Participants were asked to bisect 240 stimuli, comprising: (i) affirmative and interrogative clauses, (ii) sentences with lexical and syntactic violations, (iii) letter strings and (iv) simple lines. As predicted, neurologically intact participants showed larger leftward biases in bisecting written readable sentences compared to strings of letters. In contrast, the left hemispheredamaged patients (both with and without aphasia) showed no differences in bisecting sentences and letter strings or lines. These findings indicate that the larger leftward bias exhibited by healthy participants in the bisection of sentences is likely due to ortho-phonological coding taking place implicitly during the bisection task. This ortho-phonological coding is impaired with left brain damage - also in absence of apparent aphasia - leading to the left hemispheredamaged patients showing a reduced leftward bias in sentence bisection. These findings support the hypothesis that the leftward bias in the bisection of written sentences is the result of ortho-phonological influences rather than visual-spatial biases.

No evidence of effectiveness of mirror therapy early after stroke: an assessor-blinded randomized controlled trial.

OBJECTIVE: The aim of this study was to investigate the efficacy of mirror therapy on upper-limb recovery in early post-stroke patients. DESIGN: Assessor-blinded randomized controlled trial. SETTING: Inpatient rehabilitation clinic. SUBJECTS: A total of 40 patients with upper-limb impairment due to a first-ever ischaemic or haemorrhagic stroke, within four weeks from the cerebrovascular accident. INTERVENTION: The intervention group received mirror therapy, while the control group received sham therapy. During mirror therapy, patients' sound hand was reflected by a mirror. During sham therapy, an opaque surface replaced the mirror-reflecting surface. Both the mirror therapy and sham therapy groups practised their sound hand with exercises, ranging from the simple elbow flexion-extension to complex tasks (e.g. reaching and grasping). Mirror therapy and sham therapy were added to conventional rehabilitation. MAIN MEASURES: Primary outcome includes Fugl-Meyer upper extremity scale. Secondary outcomes include action research arm test (ARAT) and functional independence measure (FIM) scale. Outcomes were measured at the beginning (T0) and end (T1) of the treatment. RESULTS: At baseline, both groups (sham therapy vs. mirror therapy; mean (SD)) were comparable for Fugl-Meyer (30.9 (23.9) vs. 28.5 (21.8)), ARAT (25.1 (25.5) vs. 23.5 (24)) and FIM (71.0 (20.6) vs. 72.9 (17.8)) scores. At the end of the treatment, both groups significantly improved in the Fugl-Meyer (40.6 (21.3) vs. 38.3 (23.4)), ARAT (31.9 (23.0) vs. 30 (24.1)) and FIM (100.3 (21.9) vs. 99.4 (22.6)) scores. However, at T1, no significant difference was observed between the sham therapy and mirror therapy groups, neither for the Fugl-Meyer, nor for ARAT and FIM scores. CONCLUSION: Compared with sham therapy, mirror therapy did not add additional benefit to upper-limb recovery early after stroke.

"The vestibular system, body temperature and sense of body ownership: a potential link? Insights from a single case study".

The vestibular system plays a pivotal role in behavioural and physiological aspects of body representation. If on the one hand, the stimulation of the vestibular system in healthy subjects provokes body representation distortions, accompanied by a decrease of body temperature, on the other hand, in brain-damaged patients it transiently restores body representation disorders. So far, the physiological counterpart of such behavioural amelioration on patients has never been explored. Here we aimed at investigating body temperature variations following Caloric Vestibular Stimulation (CVS), in a patient affected by somatoparaphrenia who regained the sense of body part ownership after the stimulation. Results showed an increase in body temperature after CVS, which also correlated with the temporary restored sense of limb ownership. Our results support the idea that physiological signals are fundamental to maintain a coherent mental representation of the body.

Geschwind Syndrome in frontotemporal lobar degeneration: Neuroanatomical and neuropsychological features over 9 years.

Geschwind Syndrome, a characteristic behavioral syndrome frequently described in patients affected by temporal lobe epilepsy (TLE), consists of the following features: hyper-religiosity, hypergraphia, hyposexuality, and irritability. Here we report the 9-year-clinical course of a case of Geschwind Syndrome that developed as a first and salient clinical expression of right temporal lobe variant of frontotemporal lobar degeneration (FTLD). Only one patient affected by frontotemporal dementia has previously been shown to present with Geschwind Syndrome. MS presented at age 73 with 3 years of personality and behavioral symptoms. Her early symptoms primarily included hyper-religiosity, hypergraphia, and poor emotional regulation (irritability, impulsivity, disinhibition, egocentric behavior). Over nine years, other cognitive functions (word retrieval, memory coding and recall, set-shifting, famous face and building recognition) became affected; however, hyper-religiosity, hypergraphia, and scarce emotional control remained her most prominent deficits. Longitudinal cortical thickness and volumetric analyses revealed early atrophy in the right temporal pole, right amygdala, and right hippocampus, which progressively affected homologous regions in the left hemisphere. The present case describes an unusual clinical picture associated with frontotemporal dementia (FTD), in which the most salient symptoms originated and remained consistent with Geschwind Syndrome.

Motor recovery in post-stroke patients with aphasia: the role of specific linguistic abilities.

BACKGROUND: Aphasia is a serious consequence of stroke but aphasics patients have been routinely excluded from participation in some areas of stroke research. OBJECTIVE: To assess the role of specific linguistic and non-verbal cognitive abilities on the short-term motor recovery of patients with aphasia due to first-ever stroke to the left hemisphere after an intensive rehabilitation treatment. METHODS: 48 post-acute aphasic patients, who underwent physiotherapy and speech language therapy, were enrolled for this retrospective cohort-study. Four types of possible predictive factors were taken into account: clinical variables, functional status, language and non-verbal cognitive abilities. The motor FIM at discharge was used as the main dependent variable. RESULTS: Patients were classified as follows: 6 amnestic, 9 Broca's, 7 Wernicke's, and 26 global aphasics. Motor FIM at admission (p = 0.003) and at discharge (p = 0.042), all linguistic subtests of Aachener AphasieTest (p = 0.001), and non-verbal reasoning abilities (Raven's CPM, p = 0.006) resulted significantly different across different types of aphasia. Post-hoc analyses showed differences only between global aphasia and the other groups. A Multiple Linear Regression shows that admission motor FIM (p = 0.001) and Token test (p = 0.040), adjusted for clinical, language, and non-verbal reasoning variables, resulted as independent predictors of motor FIM scores at discharge, while Raven's CPM resulted close to statistical significance. CONCLUSIONS: Motor function at admission resulted as the variable that most affects the motor recovery of post-stroke patients with aphasia after rehabilitation. A linguistic test requiring also non-linguistic abilities, including attention and working memory (i.e. Token test) is an independent predictor as well.

Radial bisection of words and lines in right-brain-damaged patients with spatial neglect.

The bisection of lines positioned radially (with the two ends of the line close and far, with respect to the participant's body) has been less investigated than that of lines placed horizontally (with their two ends left and right, with respect to the body's midsagittal plane). In horizontal bisection, patients with left neglect typically show a rightward bias for both lines and words, greater with longer stimuli. As for radial bisection, available data indicate that neurologically unimpaired participants make a distal error, while results from right-brain-damaged patients with left spatial neglect are contradictory. We investigated the bisection of radially oriented words, with the prediction that, during bisection, linguistic material would be recoded to its canonical left-to-right format in reading, with the performance of neglect patients being similar to that for horizontal words. Thirteen right-brain-damaged patients (seven with left spatial neglect) and fourteen healthy controls were asked to manually bisect 40 radial and 40 horizontal words (5-10 letters), and 80 lines, 40 radial and 40 horizontal, of comparable length. Right-brain-damaged patients with spatial neglect exhibited a proximal bias in the bisection of short radial words, with the proximal part corresponding to the final right part of horizontally oriented words. This proximal error was not found in patients without neglect and healthy controls. For bisection, short radial words may be recoded to the canonical orthographic horizontal format, unveiling the impact of left neglect on radially oriented stimuli.

The spatial side of somatoparaphrenia: a case study.

The perception of the bodily self in space is a composite cognitive function requiring a dynamic integrated brain mechanism. Somatoparaphrenia (SP), a delusional belief concerning the experienced disownership for the contralesional paralyzed arm, represents the disruption of such mechanism. In two experiments, we have investigated the alteration of limb disownership after spatial manipulations in a right-brain-damaged patient affected by chronic SP. In experiment 1 the patient's spatial attention was switched between the left and right sides of space. SP signs worsened when the patient was interviewed from the left compared to the right bedside. In the second experiment we showed the first systematic transient remission of SP using left caloric vestibular stimulation (CVS), a physiologic manipulation mainly acting on the spatial frame of reference. Taken together, these results shed further light on the spatial nuance of SP and on the importance of vestibular signals for the generation of a coherent body representation. Furthermore, our case study demonstrated the possibility of eliciting more severe SP signs if the patient is interviewed from the left bedside. Additionally, CVS applications may have an important impact on the rehabilitation of these symptoms.

Combining language and space: sentence bisection in unilateral spatial neglect.

In line bisection right-brain-damaged patients with left spatial neglect show a rightward deviation, with respect to the line's physical center. In word bisection ortho-phonological features of the stimulus' final (right-sided) part modulate performance of both patients and healthy participants (Veronelli, Vallar, Marinelli, Primativo, & Arduino, 2014). We investigated the role of linguistic factors in sentence bisection, in patients with and without neglect, and control participants. The effects of information in the right-sided part of the sentence (Experiment #1), and of lexical and syntactic violations (Experiment #2) were assessed. Neglect patients showed an overall rightward bias, larger than those of patients without neglect and controls. The neglect patients' bias was modulated by stimulus type, decreasing from lines, to letter strings and to all types of sentences. In sum, in visuo-manual sentence bisection a basic linguistic mechanism, such as sentence readability, brings about a more leftward appreciation of the stimulus, reducing the neglect patients' rightward bias.