Incidental findings on brain MRI in patients with first-episode and chronic psychosis.

Brain incidental findings (IFs) are unexpected brain abnormalities detected by a structural magnetic resonance (MRI) examination. We conducted a study to assess whether brain IFs are associated with first-episode psychosis (FEP) and chronic psychosis (affective vs. non-affective) compared to healthy controls (HC). Chi-squared analyses were run to compare the frequency of several IFs across groups. Logistic regression analyses were run to explore the association between group and IFs, accounting for sex, age, MRI field strength. We observed a higher frequency of most IFs in both FEP and chronic psychosis groups compared to HC, however most of the chi-squared tests did not reach significance. Patients with FEP and chronic psychosis were 3-4 times more likely to show deep white matter hyperintensities (WMH) than HC. Patients with FEP and affective chronic psychosis were 3-4 times more likely to show ventricular asymmetries than HC. All chronic patients were more likely to show periventricular WMH, liquoral spaces enlargements and ventricular system enlargements respectively. Our results suggest that deep WMH and ventricular asymmetries are associated with both the early and the chronic stages of psychosis, thus representing potential vulnerability factors already present before the onset of the symptoms, possibly due to neurodevelopmental insults.

White matter abnormalities in the amputation variant of body integrity dysphoria.

"Body integrity dysphoria" (BID) is a severe condition affecting nonpsychotic individuals. In the amputation variant of BID, a limb may be experienced as not being part of the body, despite normal anatomical development and intact sensorimotor functions. We previously demonstrated altered brain structural (gray matter) and functional connectivity in 16 men with BID with a long-lasting and exclusive desire for left leg amputation. Here, we aimed to identify, in the same sample, altered patterns of white matter structural connectivity. Fractional anisotropy (FA), derived from diffusion tensor imaging data, was considered as a measure of structural connectivity. Results showed reduced structural connectivity of: (i) the right superior parietal lobule (rSPL) with the right cuneus, with the superior occipital and with the posterior cingulate gyri, (ii) the pars orbitalis of the right middle frontal gyrus (rMFGOrb) with the putamen, and (iii) the left middle temporal gyrus (lMTG) with the pars triangularis of the left inferior frontal gyrus. Increased connectivity was found between the right paracentral lobule (rPLC) and the right caudate nucleus. By using a complementary method of investigation, we confirmed and extended previous results from the same sample of individuals with BID, showing structural alterations between areas tuned to the processing of the sensorimotor representations of the affected leg (rPCL), and to higher-order components of bodily representation such as the body image (rSPL) and visual processing. Alongside this network for bodily awareness, other networks such as the limbic (rMFGOrb) and the mirror (lMTG) systems showed alterations in structural connectivity. These findings consolidate current understanding of the neural correlates of the amputation variant of BID, which might in turn guide diagnostics and rehabilitative treatments.

Clinical Characterization of Atypical Primary Progressive Aphasia in a 3-Year Longitudinal Study: A Case Report.

The logopenic variant of primary progressive aphasia (lvPPA) is the most recent variant of primary progressive aphasia (PPA) to be identified; thus far, it has been poorly investigated. Despite being typically associated with Alzheimer disease (AD), lvPPA has recently been linked to frontotemporal lobe degeneration (FTLD), with distinctive cognitive and neural features that are worthy of further investigation. Here, we describe the neuropsychological and linguistic profile, as well as cerebral abnormalities, of an individual exhibiting PPA and carrying a pathogenetic variant in the GRN gene, from a 3-year longitudinal perspective. The individual's initial profile resembled lvPPA because it was characterized by word-finding difficulties and phonological errors in spontaneous speech in addition to sentence repetition and phonological short-term memory impairments. The individual's structural and metabolic imaging data demonstrated left temporal and bilateral frontal atrophy and hypometabolism, respectively. On follow-up, as the pathology progressed, dysprosody, stereotypical speech patterns, agrammatism, and orofacial apraxia appeared, suggesting an overlap with the nonfluent variant of PPA (nfvPPA). Severe sentence comprehension impairment also became evident. Our longitudinal and multidisciplinary diagnostic approach allowed us to better characterize the progression of a GRN-positive lvPPA profile, providing neuropsychological and imaging indicators that might be helpful to improve classification between different PPA variants and to address a nosological issue. Finally, we discuss the importance of early diagnosis of PPA given the possible overlap between different PPA variants during the progression of the pathology.

Brain Abnormalities in Individuals with a Desire for a Healthy Limb Amputation: Somatosensory, Motoric or Both? A Task-Based fMRI Verdict.

Body integrity dysphoria (BID), a long-lasting desire for the amputation of physically healthy limbs, is associated with reduced fMRI resting-state functional connectivity of somatosensory cortices. Here, we used fMRI to evaluate whether these findings could be replicated and expanded using a task-based paradigm. We measured brain activations during somatosensory stimulation and motor tasks for each of the four limbs in ten individuals with a life-long desire for the amputation of the left leg and fourteen controls. For the left leg, BID individuals had reduced brain activation in the right superior parietal lobule for somatosensory stimulation and in the right paracentral lobule for the motor task, areas where we previously found reduced resting-state functional connectivity. In addition, for somatosensory stimulation only, we found a robust reduction in activation of somatosensory areas SII bilaterally, mostly regardless of the stimulated body part. Areas SII were regions of convergent activations for signals from all four limbs in controls to a significantly greater extent than in subjects with BID. We conclude that BID is associated with altered integration of somatosensory and, to a lesser extent, motor signals, involving limb-specific cortical maps and brain regions where the first integration of body-related signals is achieved through convergence.

Bleeding of Perivascular Spaces in Midbrain of a Young Patient With Head Trauma.

Perivascular spaces (PVSs) surrounding the walls of arteries, arterioles, and venules are a common finding in brain imaging. Even if they do not directly communicate with subarachnoid spaces, there are some cases in which subarachnoid hemorrhage (SAH) and intracerebral hematomas extend to the PVSs by leakage of the leptomeninges. In this report, we present a case of enlargement and bleeding of PVSs in the midbrain of a young woman with head trauma, without evident SAH or intracerebral hematomas.

Autonomic responses to emotional linguistic stimuli and amplitude of low-frequency fluctuations predict outcome after severe brain injury.

An accurate prognosis on the outcome of brain-injured patients with disorders of consciousness (DOC) remains a significant challenge, especially in the acute stage. In this study, we applied a multiple-technique approach to provide accurate predictions on functional outcome after 6 months in 15 acute DOC patients. Electrophysiological correlates of implicit cognitive processing of verbal stimuli and data-driven voxel-wise resting-state fMRI signals, such as the fractional amplitude of low-frequency fluctuations (fALFF), were employed. Event-related electrodermal activity, an index of autonomic activation, was recorded in response to emotional words and pseudo-words at baseline (T0). On the same day, patients also underwent a resting-state fMRI scan. Six months later (T1), patients were classified as outcome-negative and outcome-positive using a standard functional outcome scale. We then revisited the baseline measures to test their predictive power for the functional outcome measured at T1. We found that only outcome-positive patients had an earlier, higher autonomic response for words compared to pseudo-words, a pattern similar to that of healthy awake controls. Furthermore, DOC patients showed reduced fALFF in the posterior cingulate cortex (PCC), a brain region that contributes to autonomic regulation and awareness. The event-related electrodermal marker of residual cognitive functioning was found to have a significant correlation with residual local neuronal activity in the PCC. We propose that a residual autonomic response to cognitively salient stimuli, together with a preserved resting-state activity in the PCC, can provide a useful prognostic index in acute DOC.

Neural Correlates of Body Integrity Dysphoria.

There are few things as irrefutable as the evidence that our limbs belong to us. However, persons with body integrity dysphoria (BID) [1] deny the ownership of one of their fully functional limbs and seek its amputation [2]. We tapped into the brain mechanisms of BID, examining sixteen men desiring the removal of the left healthy leg. The primary sensorimotor area of the to-be-removed leg and the core area of the conscious representation of body size and shape (the right superior parietal lobule [rSPL]) [3, 4] were less functionally connected to the rest of the brain. Furthermore, the left premotor cortex, reportedly involved in the multisensory integration of limb information [5-7], and the rSPL were atrophic. The more atrophic the rSPL, the stronger the desire for amputation, and the more an individual pretended to be an amputee by using wheelchairs or crutches to solve the mismatch between the desired and actual body. Our findings illustrate the pivotal role of the connectivity of the primary sensorimotor limb area in the mediation of the feeling of body ownership. They also delineate the morphometric and functional alterations in areas of higher-order body representation possibly responsible for the dissatisfaction with a standard body configuration. The neural correlates of BID may foster the understanding of other neuropsychiatric disorders involving the bodily self. Ultimately, they may help us understand what most of us take for granted, i.e., the experience of body and self as a seamless unity.

A very light lunch: Interoceptive deficits and food aversion at onset in a case of behavioral variant frontotemporal dementia.

INTRODUCTION: Patients affected by the behavioral variant frontotemporal dementia (bvFTD) frequently experience, at a delayed onset, abnormal eating behavior involving increased food intake. Although delusional food-related symptoms have attracted much attention, the behavioral and neural features of food aversion manifestations in bvFTD remain poorly documented. METHODS: We describe the rare case of a patient with bvFTD presenting with lack of interoception for swallowing and digestion, coupled with a dramatic food aversion at onset. We also compared his MRI scan to 84 healthy individuals using a voxel-based morphometry approach. RESULTS: We found gray matter density reductions involving the postcentral gyrus bilaterally, insulae, and right medial orbitofrontal cortex. DISCUSSION: Our results shed new light on the behavioral and neuroanatomical features of food aversion and interoception deficits in bvFTD, suggesting that besides orbitofrontal cortex, also a distributed system associated with interoception might play a role in such behavioral manifestation.

How many deficits in the same dyslexic brains? A behavioural and fMRI assessment of comorbidity in adult dyslexics.

Dyslexia can have different manifestations: this has motivated different theories on its nature, on its underlying brain bases and enduring controversies on how to best treat it. The relative weight of the different manifestations has never been evaluated using both behavioural and fMRI measures, a challenge taken here to assess the major systems called into play in dyslexia by different theories. We found that adult well-compensated dyslexics were systematically impaired only in reading and in visuo-phonological tasks, while deficits for other systems (e.g., motor/cerebellar, visual magnocellular/motion perception) were only very occasional. In line with these findings, fMRI showed a reliable hypoactivation only for the task of reading, in the left occipito-temporal cortex (l-OTC). The l-OTC, normally a crossroad between the reading system and other systems, did not show the same level of intersection in dyslexics; yet, it was not totally silent because it responded, in segregated parts, during auditory phonological and visual motion perception tasks. This minimal behavioural and functional anatomical comorbidity demonstrates that a specific deficit of reading is the best description for developmental dyslexia, at least for adult well-compensated cases, with clear implications for rehabilitation strategies. The reduced intersection of multiple systems in the l-OTC suggests that dyslexics suffer from a coarser connectivity, leading to disconnection between the multiple domains that normally interact during reading.

Anatomical Modularity of Verbal Working Memory? Functional Anatomical Evidence from a Famous Patient with Short-Term Memory Deficits.

Cognitive skills are the emergent property of distributed neural networks. The distributed nature of these networks does not necessarily imply a lack of specialization of the individual brain structures involved. However, it remains questionable whether discrete aspects of high-level behavior might be the result of localized brain activity of individual nodes within such networks. The phonological loop of working memory, with its simplicity, seems ideally suited for testing this possibility. Central to the development of the phonological loop model has been the description of patients with focal lesions and specific deficits. As much as the detailed description of their behavior has served to refine the phonological loop model, a classical anatomoclinical correlation approach with such cases falls short in telling whether the observed behavior is based on the functions of a neural system resembling that seen in normal subjects challenged with phonological loop tasks or whether different systems have taken over. This is a crucial issue for the cross correlation of normal cognition, normal physiology, and cognitive neuropsychology. Here we describe the functional anatomical patterns of JB, a historical patient originally described by Warrington et al. (1971), a patient with a left temporo-parietal lesion and selective short phonological store deficit. JB was studied with the H215O PET activation technique during a rhyming task, which primarily depends on the rehearsal system of the phonological loop. No residual function was observed in the left temporo-parietal junction, a region previously associated with the phonological buffer of working memory. However, Broca's area, the major counterpart of the rehearsal system, was the major site of activation during the rhyming task. Specific and autonomous activation of Broca's area in the absence of afferent inputs from the other major anatomical component of the phonological loop shows that a certain degree of functional independence or modularity exists in this distributed anatomical-cognitive system.

Dissociation between preserved body structural description and impaired body image following a pediatric spinal trauma.

In adult patients, Spinal Cord Injury (SCI) may influence the mental Body Representation (BR). Currently, there is no evidence on the modulation of SCI on BR during early stages of cognitive development. Here, we investigated BR in a 3-year-old child with complete SCI. The patient was administered with a specific battery assessing different BR components. We found evidence for putative classical neuropsychological dissociation between a preserved topological map with impaired semantic knowledge of the body. This finding sheds new light on the impact of SCI on BR in childhood, as well as on the level of interdependence between BR's components..

A new tool for touch-free patient registration for robot-assisted intracranial surgery: application accuracy from a phantom study and a retrospective surgical series.

OBJECTIVE The purpose of this study was to compare the accuracy of Neurolocate frameless registration system and frame-based registration for robotic stereoelectroencephalography (SEEG). METHODS The authors performed a 40-trajectory phantom laboratory study and a 127-trajectory retrospective analysis of a surgical series. The laboratory study was aimed at testing the noninferiority of the Neurolocate system. The analysis of the surgical series compared Neurolocate-based SEEG implantations with a frame-based historical control group. RESULTS The mean localization errors (LE) ± standard deviations (SD) for Neurolocate-based and frame-based trajectories were 0.67 ± 0.29 mm and 0.76 ± 0.34 mm, respectively, in the phantom study (p = 0.35). The median entry point LE was 0.59 mm (interquartile range [IQR] 0.25-0.88 mm) for Neurolocate-registration-based trajectories and 0.78 mm (IQR 0.49-1.08 mm) for frame-registration-based trajectories (p = 0.00002) in the clinical study. The median target point LE was 1.49 mm (IQR 1.06-2.4 mm) for Neurolocate-registration-based trajectories and 1.77 mm (IQR 1.25-2.5 mm) for frame-registration-based trajectories in the clinical study. All the surgical procedures were successful and uneventful. CONCLUSIONS The results of the phantom study demonstrate the noninferiority of Neurolocate frameless registration. The results of the retrospective surgical series analysis suggest that Neurolocate-based procedures can be more accurate than the frame-based ones. The safety profile of Neurolocate-based registration should be similar to that of frame-based registration. The Neurolocate system is comfortable, noninvasive, easy to use, and potentially faster than other registration devices.

SUrface-PRojected FLuid-Attenuation-Inversion-Recovery Analysis: A Novel Tool for Advanced Imaging of Epilepsy.

OBJECTIVE: The objective of this pilot retrospective study is to describe the SUrface-PRojected FLuid-Attenuation-Inversion-Recovery (SUPR-FLAIR) analysis, a novel method mainly aimed at revealing cortical areas with subtle signal hyperintensity. METHODS: Images from 101 healthy controls and 10 patients suffering from drug-resistant partial epilepsy were retrospectively postprocessed. The brain surface was reconstructed from a 3-dimensional (3D) T1-weighted fast field echo (T1W-FFE) magnetic resonance imaging (MRI) scan. A turbo spin echo fluid attenuated inversion recovery axial scan was registered to the 3D T1W-FFE scan, and its intensity values were normalized. The cortical intensity signal was projected onto the brain surface, and surface-based analysis was performed, comparing each patient against the 101 controls. The localizations of the first positive lower P value cluster (PLPC) peak and the resection zone (RZ) were compared. We studied 5 patients with focal cortical dysplasia (3 of them with negative MRI) and 5 with hippocampal sclerosis. RESULTS: SUPR-FLAIR analysis localized the first PLPC peak in the RZ in all cases. Because all patients have been seizure free since surgery, it can be assumed that the epileptogenic zone (EZ) was included in the RZ. Therefore, SUPR-FLAIR analysis correctly aligned with the EZ, with 100% sensitivity. CONCLUSIONS: SUPR-FLAIR analysis is a noninvasive technique that could be helpful for the definition of the EZ, especially when MRI is negative. Its use could reduce the indications for invasive electroencephalography or could provide essential data to refine the strategy of intracerebral electrode implantation in the most challenging cases.

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.

Framing effects reveal discrete lexical-semantic and sublexical procedures in reading: an fMRI study.

According to the dual-route model, a printed string of letters can be processed by either a grapheme-to-phoneme conversion (GPC) route or a lexical-semantic route. Although meta-analyses of the imaging literature support the existence of distinct but interacting reading procedures, individual neuroimaging studies that explored neural correlates of reading yielded inconclusive results. We used a list-manipulation paradigm to provide a fresh empirical look at this issue and to isolate specific areas that underlie the two reading procedures. In a lexical condition, we embedded disyllabic Italian words (target stimuli) in lists of either loanwords or trisyllabic Italian words with unpredictable stress position. In a GPC condition, similar target stimuli were included within lists of pseudowords. The procedure was designed to induce participants to emphasize either the lexical-semantic or the GPC reading procedure, while controlling for possible linguistic confounds and keeping the reading task requirements stable across the two conditions. Thirty-three adults participated in the behavioral study, and 20 further adult participants were included in the fMRI study. At the behavioral level, we found sizeable effects of the framing manipulations that included slower voice onset times for stimuli in the pseudoword frames. At the functional anatomical level, the occipital and temporal regions, and the intraparietal sulcus were specifically activated when subjects were reading target words in a lexical frame. The inferior parietal and anterior fusiform cortex were specifically activated in the GPC condition. These patterns of activation represented a valid classifying model of fMRI images associated with target reading in both frames in the multi-voxel pattern analyses. Further activations were shared by the two procedures in the occipital and inferior parietal areas, in the premotor cortex, in the frontal regions and the left supplementary motor area. These regions are most likely involved in either early input or late output processes.

Unrealistic representations of "the self": A cognitive neuroscience assessment of anosognosia for memory deficit.

Three cognitive components may play a crucial role in both memory awareness and in anosognosia for memory deficit (AMD): (1) a personal data base (PDB), i.e., a memory store that contains "semantic" representations about the self, (2) monitoring processes (MPs) and (3) an explicit evaluation system (EES), or comparator, that assesses and binds the representations stored in the PDB with information obtained from the environment. We compared both the behavior and the functional connectivity (as assessed by resting-state fMRI) of AMD patients with aware patients and healthy controls. We found that AMD is associated with an impoverished PDB, while MPs are necessary to successfully update the PDB. AMD was associated with reduced functional connectivity within both the default-mode network and in a network that includes the left lateral temporal cortex, the hippocampus and the insula. The reduced connectivity between the hippocampus and the insular cortex was correlated with AMD severity.

The physiology of motor delusions in anosognosia for hemiplegia: implications for current models of motor awareness.

Right brain damaged patients sometimes deny that their left arm is paralysed or even claim to have just moved it. This condition is known as anosognosia for hemiplegia (AHP). Here, we used fMRI to study patients with and without AHP during the execution of a motor task. We found that the delusional belief of having moved was preceded by brain activation of the cortical regions that are implicated in motor control in the left intact hemisphere and in the spared motor regions of the right hemisphere; patients without anosognosia did not present with the same degree of activation. We conclude that the false belief of movement is associated with a combination of strategically placed brain lesions and the preceding residual neural activity of the fronto-parietal motor network. These findings provide evidence that the activity of motor cortices contributes to our beliefs about the state of our motor system.

How many forms of perseveration? Evidence from cancellation tasks in right hemisphere patients.

Neglect patients' performance during cancellation tasks is characterized by left sided omissions and, in many cases, by the production of inappropriate material of various kinds in the ipsilesional space, e.g. additional marks over already cancelled targets, marks drawn away from targets, scribbles, irrelevant drawings. It is unclear whether these behaviours, which have collectively been called perseverative, are functionally and anatomically connected and whether they correlate with the severity of neglect. Here we report a retrospective study on 33 right brain damaged patients with neglect after right hemisphere lesions in whom we measured the intensity of perseveration of the three following kinds: (1) 'additional marks' (AM) perseveration where patients cancelled a target with two or more well separated marks; (2) 'scribble' perseveration, where patients, instead of cancelling the target with a single pen stroke as required by the task, performed multiple pen strokes without breaking the pen-to-paper contact, with the final product being a scribble; (3) 'flying marks' (FM) perseveration where patients produced cancellation marks well away from the targets. We found that AM and FM perseveration correlated with neglect severity, while 'scribble' perseveration did not. The lesion-symptom mapping showed three separate anatomical areas in the right hemisphere: 'scribble' perseveration was associated with lesions of the orbitofrontal cortex and caudate nucleus; AM perseveration was associated with damage to the rolandic operculum, superior temporal gyrus and inferior frontal gyrus; FM perseveration was associated with damage to the dorsal premotor cortex and the temporal pole. Neglect severity followed damage to a region which grossly corresponds to the sum of the regions associated with AM and FM perseveration respectively. This complex behavioural and anatomical pattern is interpreted in terms of a three-factor model, in which AM perseveration is caused by a deficit of disengagement of attention from the right side (also causing omissions), FM perseveration is caused by directional hypokinesia (also causing left-side omissions), and 'scribble' perseveration is the consequence of a failure to inhibit an initiated motor act, which is completely separate (both anatomically and functionally) from the disorder inducing omissions.

Is a lone right hemisphere enough? Neurolinguistic architecture in a case with a very early left hemispherectomy.

We studied the linguistic profile and neurolinguistic organization of a 14-year-old adolescent (EB) who underwent a left hemispherectomy at the age of 2.5 years. After initial aphasia, his language skills recovered within 2 years, with the exception of some word finding problems. Over the years, the neuropsychological assessments showed that EB's language was near-to-normal, with the exception of lexical competence, which lagged slightly behind for both auditory and written language. Moreover, EB's accuracy and speed in both reading and writing words and non-words were within the normal range, whereas difficulties emerged in reading loan words and in tasks with homophones. EB's functional magnetic resonance imaging (fMRI) patterns for several linguistic and metalinguistic tasks were similar to those observed in the dominant hemisphere of controls, suggesting that his language network conforms to a left-like linguistic neural blueprint. However, a stronger frontal recruitment suggests that linguistic tasks are more demanding for him. Finally, no specific reading activation was found in EB's occipitotemporal region, a finding consistent with the surface dyslexia-like behavioral pattern of the patient. While a lone right hemisphere may not be sufficient to guarantee full blown linguistic competences after early hemispherectomy, EB's behavioral and fMRI patterns suggest that his lone right hemisphere followed a left-like blueprint of the linguistic network.