The Precentral Insular Cortical Network for Speech Articulation.

Apraxia of speech is a motor disorder characterized by the impaired ability to coordinate the sequential articulatory movements necessary to produce speech. The critical cortical area(s) involved in speech apraxia remain controversial because many of the previously reported cases had additional aphasic impairments, preventing localization of the specific cortical circuit necessary for the somatomotor execution of speech. Four patients with "pure speech apraxia" (i.e., who had no aphasic and orofacial motor impairments) are reported here. The critical lesion in all four patients involved, in the left hemisphere, the precentral gyrus of the insula (gyrus brevis III) and, to a lesser extent, the nearby areas with which it is strongly connected: the adjacent subcentral opercular cortex (part of secondary somatosensory cortex) and the most inferior part of the central sulcus where the orofacial musculature is represented. There was no damage to rostrally adjacent Broca's area in the inferior frontal gyrus. The present study demonstrates the critical circuit for the coordination of complex articulatory movements prior to and during the execution of the motor speech plans. Importantly, this specific cortical circuit is different from those that relate to the cognitive aspects of language production (e.g., Broca's area on the inferior frontal gyrus).

Perceiving numerosity does not cause automatic shifts of spatial attention.

It is debated whether the representation of numbers is endowed with a directional-spatial component so that perceiving small-magnitude numbers triggers leftward shifts of attention and perceiving large-magnitude numbers rightward shifts. Contrary to initial findings, recent investigations have demonstrated that centrally presented small-magnitude and large-magnitude Arabic numbers do not cause leftward and rightward shifts of attention, respectively. Here we verified whether perceiving small or large non-symbolic numerosities (i.e., clouds of dots) drives attention to the left or the right side of space, respectively. In experiment 1, participants were presented with central small (1, 2) vs large-numerosity (8, 9) clouds of dots followed by an imperative target in the left or right side of space. In experiment 2, a central cloud of dots (i.e., five dots) was followed by the simultaneous presentation of two identical dot-clouds, one on the left and one on the right side of space. Lateral clouds were both lower (1, 2) or higher in numerosity (8, 9) than the central cloud. After a variable delay, one of the two lateral clouds turned red and participants had to signal the colour change through a unimanual response. We found that (a) in Experiment 1, the small vs large numerosity of the central cloud of dots did not speed up the detection of left vs right targets, respectively, (b) in Experiment 2, the detection of colour change was not faster in the left side of space when lateral clouds were smaller in numerosity than the central reference and in the right side when clouds were larger in numerosity. These findings show that perceiving non-symbolic numerosity does not cause automatic shifts of spatial attention and suggests no inherent association between the representation of numerosity and that of directional space.

A Scoping Review of Neuromodulation Techniques in Neurodegenerative Diseases: A Useful Tool for Clinical Practice?

Background and Objectives: Neurodegenerative diseases that typically affect the elderly such as Alzheimer's disease, Parkinson's disease and frontotemporal dementia are typically characterised by significant cognitive impairment that worsens significantly over time. To date, viable pharmacological options for the cognitive symptoms in these clinical conditions are lacking. In recent years, various studies have employed neuromodulation techniques to try and contrast patients' decay. Materials and Methods: We conducted an in-depth literature review of the state-of-the-art of the contribution of these techniques across these neurodegenerative diseases. Results: The present review reports that neuromodulation techniques targeting cognitive impairment do not allow to draw yet any definitive conclusion about their clinical efficacy although preliminary evidence is very encouraging. Conclusions: Further and more robust studies should evaluate the potentialities and limitations of the application of these promising therapeutic tools to neurodegenerative diseases.

The Hemispheric Distribution of α-Band EEG Activity During Orienting of Attention in Patients with Reduced Awareness of the Left Side of Space (Spatial Neglect).

EEG studies in healthy humans have highlighted that alpha-band activity is relatively reduced over the occipital-parietal areas of the hemisphere contralateral to the direction of spatial attention. Here, we investigated the hemispheric distribution of alpha during orienting of attention in male and female right brain-damaged patients with left spatial neglect. Temporal spectral evolution showed that in patients with neglect alpha oscillations over the damaged hemisphere were pathologically enhanced both during the baseline-fixation period that preceded cued orienting (capturing tonic alpha changes) and during orienting with leftward, rightward, or neutral-bilateral spatial cues (reflecting phasic alpha changes). Patients without neglect showed a similar though significantly less enhanced hemispheric asymmetry. Healthy control subjects displayed a conventional decrease of alpha activity over the hemisphere contralateral to the direction of orienting. In right-brain-damaged patients, neglect severity in the line bisection task was significantly correlated both with tonic alpha asymmetry during the baseline period and with phasic asymmetries during orienting of attention with neutral-bilateral and leftward cues. Asymmetries with neutral-bilateral and leftward cues were correlated with lesion of white matter tracts linking frontal with parietal-occipital areas. These findings show that disruption of rostrocaudal white matter connectivity in the right hemisphere interferes with the maintenance of optimal baseline tonic levels of alpha and the phasic modulation of alpha activity during shifts of attention. The hemispheric distribution of alpha activity can be used as a diagnostic tool for acquired pathological biases of spatial attention due to unilateral brain damage.SIGNIFICANCE STATEMENT Alpha desynchronization over the hemisphere contralateral to the attended side of space is a reliable marker of attentional orienting in the healthy human brain: can the same marker be used to spot and quantify acquired disturbances of spatial attention after unilateral brain injuries? Are pathological modifications in the hemispheric distribution of alpha specifically linked to attentional neglect for one side of space? We show that in patients with right brain damage the pathological enhancement of alpha oscillations over the parietal and occipital areas of the injured hemisphere is correlated with reduced awareness for the left side of space and with the lesion of white matter pathways that subserve frontal modulation of alpha activity in posterior brain areas.

Deconstructing Reorienting of Attention: Cue Predictiveness Modulates the Inhibition of the No-target Side and the Hemispheric Distribution of the P1 Response to Invalid Targets.

Orienting of attention produces a "sensory gain" in the processing of visual targets at attended locations and an increase in the amplitude of target-related P1 and N1 ERPs. P1 marks gain reduction at unattended locations; N1 marks gain enhancement at attended ones. Lateral targets that are preceded by valid cues also evoke a larger P1 over the hemisphere contralateral to the no-target side, which reflects inhibition of this side of space [Slagter, H. A., Prinssen, S., Reteig, L. C., & Mazaheri, A. Facilitation and inhibition in attention: Functional dissociation of pre-stimulus alpha activity, P1, and N1 components. Neuroimage, 125, 25-35, 2016]. To clarify the relationships among cue predictiveness, sensory gain, and the inhibitory P1 response, we compared cue- and target-related ERPs among valid, neutral, and invalid trials with predictive (80% valid/20% invalid) or nonpredictive (50% valid/50% invalid) directional cues. Preparatory facilitation over the visual cortex contralateral to the cued side of space (lateral directing attention positivity component) was reduced during nonpredictive cueing. With predictive cues, the target-related inhibitory P1 was larger over the hemisphere contralateral to the no-target side not only in response to valid but also in response to neutral and invalid targets: This result highlights a default inhibitory hemispheric asymmetry that is independent from cued orienting of attention. With nonpredictive cues, valid targets reduced the amplitude of the inhibitory P1 over the hemisphere contralateral to the no-target side whereas invalid targets enhanced the amplitude of the same inhibitory component. Enhanced inhibition was matched with speeded reorienting to invalid targets and drop in attentional costs. These findings show that reorienting of attention is modulated by the combination of cue-related facilitatory and target-related inhibitory activity.

Spatial uncertainty improves the distribution of visual attention and the availability of sensory information for conscious report.

Picking-up and exploiting spatial and temporal regularities in the occurrence of sensory events is important for goal-directed behaviour. According to the "Predictive Coding Hypothesis" (Friston Philosophical Trans R Soc B 360(1456):815-836, 2005), these regularities are used to generate top-down predictions that are constantly compared with actual sensory events. In a previous study with the Attentional Blink (AB) paradigm, we showed that the temporal and probabilistic uncertainty of T2s that are presented outside the Attentional Blink period, i.e. at least 400 ms after T1, improves the conscious report of T2 that are presented inside the AB. The study of ERP correlated showed that this improvement was associated with a prolonged storage of pre-conscious T2 traces in extra-striate areas (Lasaponara et al. Cortex 71:15-33, 2015). Here, we tested whether variations in the probabilistic cueing of the position of a primary T1 visual target in a 4 × 4 letter array, modulate the retention of memory traces evoked by secondary letter targets (T2) that were presented in other positions of the array. Most important, in each trial, the identity of T2 was specified to participants upon disappearance of the array. We show that high probabilistic cueing facilitates T1 detection and improves the corresponding sensitivity index (d'). In contrast, retention and conscious report of secondary targets (T2) improves when the probabilistic cueing of T1 position is poor. These results suggest that uncertainty in the upcoming position of primary targets boosts the strength of memory traces evoked by secondary targets and improves the possibility that traces of secondary targets gain full access to conscious processing.

EEG Correlates of Preparatory Orienting, Contextual Updating, and Inhibition of Sensory Processing in Left Spatial Neglect.

Studies with event-related potentials have highlighted deficits in the early phases of orienting to left visual targets in right-brain-damaged patients with left spatial neglect (N+). However, brain responses associated with preparatory orienting of attention, with target novelty and with the detection of a match/mismatch between expected and actual targets (contextual updating), have not been explored in N+. Here in a study in healthy humans and brain-damaged patients of both sexes we demonstrate that frontal activity that reflects supramodal mechanisms of attentional orienting (Anterior Directing Attention Negativity, ADAN) is entirely spared in N+. In contrast, posterior responses that mark the early phases of cued orienting (Early Directing Attention Negativity, EDAN) and the setting up of sensory facilitation over the visual cortex (Late Directing Attention Positivity, LDAP) are suppressed in N+. This uncoupling is associated with damage of parietal-frontal white matter. N+ also exhibit exaggerated novelty reaction to targets in the right side of space and reduced novelty reaction for those in the left side (P3a) together with impaired contextual updating (P3b) in the left space. Finally, we highlight a drop in the amplitude and latency of the P1 that over the left hemisphere signals the early blocking of sensory processing in the right space when targets occur in the left one: this identifies a new electrophysiological marker of the rightward attentional bias in N+. The heterogeneous effects and spatial biases produced by localized brain damage on the different phases of attentional processing indicate relevant functional independence among their underlying neural mechanisms and improve the understanding of the spatial neglect syndrome.SIGNIFICANCE STATEMENT Our investigation answers important questions: are the different components of preparatory orienting (EDAN, ADAN, LDAP) functionally independent in the healthy brain? Is preparatory orienting of attention spared in left spatial neglect? Does the sparing of preparatory orienting have an impact on deficits in reflexive orienting and in the assignment of behavioral relevance to the left space? We show that supramodal preparatory orienting in frontal areas is entirely spared in neglect patients though this does not counterbalance deficits in preparatory parietal-occipital activity, reflexive orienting, and contextual updating. This points at relevant functional dissociations among different components of attention and suggests that improving voluntary attention in N+ might be behaviorally ineffective unless associated with stimulations boosting the response of posterior parietal-occipital areas.

Expectancy modulates pupil size both during endogenous orienting and during re-orienting of spatial attention: A study with isoluminant stimuli.

We have recently demonstrated that when endogenous orienting of spatial attention is guided by central directional cues that reliably predict the position of lateral targets. Pupil Dilation (PDil) is higher as compared with directional cues that do not predict target position. These findings were interpreted as reflecting different levels of Locus Coeruleus-Noradrenergic activity during endogenous orienting. In contrast to this, we were not able to highlight reliable differences between PDil responses to infrequent invalid targets that are associated with predictive cues and frequent invalid targets that are associated with non-predictive ones. These null findings might have been due to the spurious influence of transitory changes in luminance at the moment of target presentation or to the short time window used for the analysis of target-related changes in PDil. Here, we re-explored cue- and target-related changes in PDil using cue and target stimuli that were kept isoluminant to their background and long lasting cue and target periods for data recording and analysis. We fully replicate our previous cue-related results and, in addition, we demonstrate that infrequent invalid targets in the predictive experimental condition evoke larger PDil as compared with frequent ones. Analyses with Linear Mixed Models highlighted that both during the cue and target period, higher levels of PDil were associated with slower reaction times. These findings confirm that PDil is a reliable marker of the expectancy components of endogenous cue-related and exogenous target-related orienting of spatial attention.

The Attentional-SNARC effect 16 years later: no automatic space-number association (taking into account finger counting style, imagery vividness, and learning style in 174 participants).

The Attentional-SNARC effect (Att-SNARC) originally described by Fischer et al. (Nat Neurosci 6(6):555, 2003), consists of faster RTs to visual targets in the left side of space when these are preceded by small-magnitude Arabic cues at central fixation and by faster RTs to targets in the right side of space when these are preceded by large-magnitude cues. Verifying the consistency and reliability of this effect is important, because the effect would suggest an inherent association between the representation of space and that of number magnitude, while a number of recent studies provided no positive evidence in favour of the Att-SNARC and the inherency of this association (van Dijck et al. in Q J Exp Psychol 67(8):1500-1513, 2014; Zanolie and Pecher in Front Psychol 5:987, 2014; Fattorini et al. in Cortex 73:298-316, 2015; Pinto et al. in Cortex, DOI:10.1016/j.cortex.2017.12.015, 2018). Here, we re-analysed Att-SNARC data that we have collected in 174 participants over different studies run in our laboratory. Most important, in a subsample of 79 participants, we also verified whether the strength and reliability of the Att-SNARC is eventually linked inter-individual variations in finger counting style, imagery vividness, and verbal/visual learning style. We found no evidence for the Att-SNARC effect or for the influence of finger counting style, imagery vividness, and learning style on its direction or consistency. These results confirm no inherent link between orienting of spatial attention and representation of number magnitudes. We propose that this link is rather determined by the joint use of spatial and number magnitude or parity codes in the performance of the numerical task at hand.

The Response of the Left Ventral Attentional System to Invalid Targets and its Implication for the Spatial Neglect Syndrome: a Multivariate fMRI Investigation.

In humans, invalid visual targets that mismatch spatial expectations induced by attentional cues are considered to selectively engage a right hemispheric "reorienting" network that includes the temporal parietal junction (TPJ), the inferior frontal gyrus (IFG), and the medial frontal gyrus (MFG). However, recent findings suggest that this hemispheric dominance is not absolute and that it is rather observed because the TPJ and IFG areas in the left hemisphere are engaged both by invalid and valid cued targets. Because of this, the BOLD response of the left hemisphere to invalid targets is usually cancelled out by the standard "invalid versus valid" contrast used in functional magnetic resonance imaging investigations of spatial attention. Here, we used multivariate pattern recognition analysis (MVPA) to gain finer insight into the role played by the left TPJ and IFG in reorienting to invalid targets. We found that in left TPJ and IFG blood oxygen level-dependent (BOLD) responses to invalid and valid targets were associated to different patterns of neural activity, possibly reflecting the presence of functionally distinct neuronal populations. Pattern segregation was significant at group level, it was present in almost all of the participants to the study and was observed both for targets in the left and right side of space. A control whole-brain MVPA ("Searchlight" analysis) confirmed the results obtained in predefined regions of interest and highlighted that also other areas, that is, superior parietal and frontal-polar cortex, show different patterns of BOLD response to valid and invalid targets. These results confirm and expand previous evidence highlighting the involvement of the left hemisphere in reorienting of visual attention (Doricchi et al. 2010; Dragone et al. 2015). These findings suggest that asymmetrical reorienting deficits suffered by right brain damaged patients with left spatial neglect, who have severe impairments in contralesional reorienting and less severe impairments in ipsilesional reorienting, are due to preserved reorienting abilities in the intact left hemisphere.

Exploring the Interplay of Working Memory, Apathy, and Mood/Emotional Factors.

BACKGROUND: Previous investigations on healthy humans showed conflicting evidence regarding the impact of mood on working memory performance. A systematic investigation of how mood affects apathy levels in healthy participants is currently missing. METHODS: We administered a visuospatial (VS) and a numerical (N) n-back task to a sample of 120 healthy individuals. In these participants, using a series of questionnaires, we also evaluated apathy, mood, working memory, perceived stress, PTSD symptoms caused by the COVID-19 pandemic outbreak, and general psychiatric symptoms. Successively, we investigated their performance in the n-back task as a function of scores to these questionnaires. RESULTS: Participants performed better in the N block than in the VS one. Their accuracy decreased as a function of the n-back difficulty. We reported no differences in working memory performance or apathy as a function of mood, stress, or PTSD symptoms. We found that phobic anxiety negatively predicted accuracy to the numerical n-back task and that subjects with greater anxiety and difficulty in regulating emotions also showed higher levels of withdrawal from the task. CONCLUSION: The study's results suggest that while mood did not significantly affect working memory performance, strong associations were found between WMQ scores and working memory capabilities.

The time course of the spatial representation of 'past' and 'future' concepts: New evidence from the STEARC effect.

Humans use space to think of and communicate the flow of time. This spatial representation of time is influenced by cultural habits so that in left-to-right reading cultures, short durations and past events are mentally positioned to the left of long durations and future events. The STEARC effect (Space Temporal Association of Response Codes) shows a faster classification of short durations/past events with responses on the left side of space and of long durations/future events with responses on the right side. We have recently showed that during the classification of time durations, space is a late heuristic of time because in this case, the STEARC appears only when manual responses are slow, not when they are fast. Here, we wished to extend this observation to the semantic classification of words as referring to the 'past' or the 'future'. We hypothesised that the semantic processing of 'past' and 'future' concepts would have engaged slower decision processes than the classification of short versus long time durations. According to dual-route models of conflict tasks, if the task-dependent classification/decision process were to proceed relatively slowly, then the effects of direct activation of culturally preferred links between stimulus and response (S-R), i.e., past/left and future/right in the case of the present task, should attain higher amplitudes before the instruction-dependent correct response is selected. This would imply that, at variance with the faster classification of time durations, during the slower semantic classification of time concepts, in incongruent trials, the direct activation of culturally preferred S-R links should introduce significant reaction time (RT) costs and a corresponding STEARC at the fastest manual responses in the experiment too. The study's results confirmed this hypothesis and showed that in the classification of temporal words, the STEARC also increased as a function of the length of RTs. Taken together, the results from sensory duration and semantic classification STEARC tasks show that the occurrence, strength and time course of the STEARC varies significantly as a function of the speed and level of cognitive processing required in the task.

Temperament and probabilistic predictive coding in visual-spatial attention.

Cholinergic (Ach), Noradrenergic (NE), and Dopaminergic (DA) pathways play an important role in the regulation of spatial attention. The same neurotransmitters are also responsible for inter-individual differences in temperamental traits. Here we explored whether biologically defined temperamental traits determine differences in the ability to orient spatial attention as a function of the probabilistic association between cues and targets. To this aim, we administered the Structure of Temperament Questionnaire (STQ-77) to a sample of 151 participants who also performed a Posner task with central endogenous predictive (80 % valid/20 % invalid) or non-predictive cues (50 % valid/50 % invalid). We found that only participants with high scores in Plasticity and Intellectual Endurance showed a selective abatement of attentional costs with non-predictive cues. In addition, stepwise regression showed that costs in the non-predictive condition were negatively predicted by scores in Plasticity and positively predicted by scores in Probabilistic Thinking. These results show that stable temperamental characteristics play an important role in defining the inter-individual differences in attentional behaviour, especially in the presence of different probabilistic organisations of the sensory environment. These findings emphasize the importance of considering temperamental and personality traits in social and professional environments where the ability to control one's attention is a crucial functional skill.

A Reinforcement Meta-Learning framework of executive function and information demand.

Gathering information is crucial for maximizing fitness, but requires diverting resources from searching directly for primary rewards to actively exploring the environment. Optimal decision-making thus maximizes information while reducing effort costs, but little is known about the neuro-computational implementation of this tradeoff. We present a Reinforcement Meta-Learning (RML) computational model that solves the trade-off between the value and costs of gathering information. We implement the RML in a biologically plausible architecture that links catecholaminergic neuromodulators, the medial prefrontal cortex and topographically organized visual maps and show that it accounts for neural and behavioral findings on information demand motivated by instrumental incentives and intrinsic utility. Moreover, the utility function used by the RML, encoded by dopamine, is an approximation of variational free energy. Thus, the RML presents a biologically plausible mechanism for coordinating motivational, executive and sensory systems generate visual information gathering policies that minimize free energy.

How time gets spatial: factors determining the stability and instability of the mental time line.

Left-to-right readers classify faster past events with motor responses on the left side of space and future events with responses on the right side. This suggests a left-to-right spatial organization in the mental representation of time. Here, we show that the significance and reliability of this representation are linked to the joint use of temporal and spatial codes in the task at hand. In a first unimanual Go/No-Go Implicit Association Test (IAT), attending selectively to "past" or to "future" words did not activate corresponding "left" or "right" spatial concepts and vice versa. In a second IAT, attending to both temporal (i.e., "past" and "future") words and spatial targets (i.e., "left" and "right") pointing arrows produced faster responses for congruent rather than incongruent combinations of temporal and spatial concepts in task instructions (e.g., congruent = "Go with past words and left-pointing arrows"; incongruent = "Go with past words and right-pointing arrows"). This effect increased markedly in a STEARC task where spatial codes defined the selection between "left-side" and "right-side" button presses that were associated with "past" and "future" words. Two control experiments showed only partial or unreliable space-time congruency effects when (a) participants attended to superordinate semantic codes that included both spatial "left"/"right" or temporal "past/future" subordinate codes; (b) a primary speeded response was assigned to one dimension (e.g., "past vs. future") and a nonspeeded one to the other dimension (e.g., "left" vs. "right"). These results help to define the conditions that trigger a stable and reliable spatial representation of time-related concepts.

Space is a late heuristic of elapsing time: New evidence from the STEARC effect.

To get a concrete representation of its intangible flow, culture frames elapsing time along spatially oriented mental or graphical lines, which are organised according to reading habits, from left to right in western cultures. One of the strongest evidence for this spatial representation of time is the STEARC effect (Spatial-Temporal Association of Response Codes), which consists of faster coding of "short" durations with motor responses in the left side of space and of "long" durations with responses in the right side. Here, we investigated the STEARC as a function of response speed in two different experiments in healthy participants. Surprisingly, in both sub- and supra-second ranges, we found the STEARC only when decisions on time durations were slow, while no spatial representation of time was present with fast decisions. This first demonstrates that space slowly takes over faster non-spatial processing of time flow and that it is possible to empirically separate the behavioural manifestations of the non-spatial and the nurtured spatial mechanisms of time coding.

Left and right temporal-parietal junctions (TPJs) as "match/mismatch" hedonic machines: A unifying account of TPJ function.

Experimental and theoretical studies have tried to gain insights into the involvement of the Temporal Parietal Junction (TPJ) in a broad range of cognitive functions like memory, attention, language, self-agency and theory of mind. Recent investigations have demonstrated the partition of the TPJ in discrete subsectors. Nonetheless, whether these subsectors play different roles or implement an overarching function remains debated. Here, based on a review of available evidence, we propose that the left TPJ codes both matches and mismatches between expected and actual sensory, motor, or cognitive events while the right TPJ codes mismatches. These operations help keeping track of statistical contingencies in personal, environmental, and conceptual space. We show that this hypothesis can account for the participation of the TPJ in disparate cognitive functions, including "humour", and explain: a) the higher incidence of spatial neglect in right brain damage; b) the different emotional reactions that follow left and right brain damage; c) the hemispheric lateralisation of optimistic bias mechanisms; d) the lateralisation of mechanisms that regulate routine and novelty behaviours. We propose that match and mismatch operations are aimed at approximating "free energy", in terms of the free energy principle of decision-making. By approximating "free energy", the match/mismatch TPJ system supports both information seeking to update one's own beliefs and the pleasure of being right in one's own' current choices. This renewed view of the TPJ has relevant clinical implications because the misfunctioning of TPJ-related "match" and "mismatch" circuits in unilateral brain damage can produce low-dimensional deficits of active-inference and predictive coding that can be associated with different neuropsychological disorders.

Splenial Callosal Disconnection in Right Hemianopic Patients Induces Right Visual-Spatial Neglect.

Posterior cerebral artery (PCA) territory infarction involving occipital cortical damage can give rise to contralateral homonymous hemianopia. Here, we report two rare cases of patients with lesions in the left hemisphere PCA territory who developed right visuo-spatial neglect. One patient suffered right hemianopia and right visuo-spatial neglect after a stroke that damaged the left primary visual cortex and the callosal splenial fibers. The other unique case is of a patient who had a brain tumor in the posterior cerebral region in the left hemisphere and initially exhibited only right hemianopia that developed into right visuo-spatial neglect after tumor resection that included the splenial fibers. These cases indicate that, as in cases with damage in the right PCA territory, lesions in the left PCA yield visuo-spatial neglect when the damage produces contralateral hemianopia and concomitant disconnection of the splenium of the corpus callosum, which interferes with the arrival of visual inputs from the intact right to the lesioned left hemisphere. These results also emphasize the necessity of sparing the splenial fibers in surgical interventions in patients who exhibit hemianopia.

A Scoping Review of Cognitive Training in Neurodegenerative Diseases via Computerized and Virtual Reality Tools: What We Know So Far.

Most prevalent neurodegenerative diseases such as Alzheimer's disease, frontotemporal dementia, Parkinson's disease and multiple sclerosis are heterogeneous in their clinical profiles and underlying pathophysiology, although they typically share the presence of cognitive impairment that worsens significantly during the course of the disease. Viable pharmacological options for cognitive symptoms in these clinical conditions are currently lacking. In recent years, several studies have started to apply Computerized Cognitive Training (CCT) and Virtual Reality (VR) tools to try and contrast patients' cognitive decay over time. However, no in-depth literature review of the contribution of these promising therapeutic options across main neurodegenerative diseases has been conducted yet. The present paper reports the state-of-the-art of CCT and VR studies targeting cognitive impairment in most common neurodegenerative conditions. Our twofold aim is to point out the scientific evidence available so far and to support health professionals to consider these promising therapeutic tools when planning rehabilitative interventions, especially when the access to regular and frequent hospital consultations is not easy to be provided.

Forgetting Unwanted Memories: Active Forgetting and Implications for the Development of Psychological Disorders.

Intrusive memories are a common feature of many psychopathologies, and suppression-induced forgetting of unwanted memories appears as a critical ability to preserve mental health. In recent years, biological and cognitive studies converged in revealing that forgetting is due to active processes. Recent neurobiological studies provide evidence on the active role of main neurotransmitter systems in forgetting, suggesting that the brain actively works to suppress retrieval of unwanted memories. On the cognitive side, there is evidence that voluntary and involuntary processes (here termed "intentional" and "incidental" forgetting, respectively) contribute to active forgetting. In intentional forgetting, an inhibitory control mechanism suppresses awareness of unwanted memories at encoding or retrieval. In incidental forgetting, retrieval practice of some memories involuntarily suppresses the retrieval of other related memories. In this review we describe recent findings on deficits in active forgetting observed in psychopathologies, like post-traumatic stress disorder, depression, schizophrenia, and obsessive-compulsive disorder. Moreover, we report studies in which the role of neurotransmitter systems, known to be involved in the pathogenesis of mental disorders, has been investigated in active forgetting paradigms. The possibility that biological and cognitive mechanisms of active forgetting could be considered as hallmarks of the early onset of psychopathologies is also discussed.