Dutch Diagnostic Instrument for Mild Aphasia (DIMA): standardisation and a first clinical application in two brain tumour patients.

Brain tumour patients with mild language disturbances are typically underdiagnosed due to lack of sensitive tests leading to negative effects in daily communicative and social life. We aim to develop a Dutch standardised test-battery, the Diagnostic Instrument for Mild Aphasia (DIMA) to detect characteristics of mild aphasia at the main linguistic levels phonology, semantics and (morpho-)syntax in production and comprehension. We designed 4 DIMA subtests: 1) repetition (words, non-words, compounds and sentences), 2) semantic odd-picture-out (objects and actions), 3) sentence completion and 4) sentence judgment (accuracy and reaction time). A normative study was carried out in a healthy Dutch-speaking population (N = 211) divided into groups of gender, age and education. Clinical application of DIMA was demonstrated in two brain tumour patients (glioma and meningioma). Standard language tests were also administered: object naming, verbal fluency (category and letter), and Token Test. Performance was at ceiling on all sub-tests, except semantic odd-picture-out actions, with an effect of age and education on most subtests. Clinical application DIMA: repetition was impaired in both cases. Reaction time in the sentence judgment test (phonology and syntax) was impaired (not accuracy) in one patient. Standard language tests: category fluency was impaired in both cases and object naming in one patient. The Token Test was not able to detect language disturbances in both cases. DIMA seems to be sensitive to capture mild aphasic deficits. DIMA is expected to be of great potential for standard assessment of language functions in patients with also other neurological diseases than brain tumours.

Dynamic causal modeling of the effective connectivity between the cerebrum and cerebellum in social mentalizing across five studies.

In this analysis we explored the effective connectivity of the cerebellum with the cerebrum in social mentalizing, across five studies (n = 91) involving abstract and complex forms of mentalizing, such as (a) person and group impression formation, based on behavioral descriptions, and (b) constructing personal counterfactual events. Connectivity was analyzed by applying dynamic causal model analysis, which revealed effective connectivity between the mentalizing areas of the cerebellum and cerebrum. The results revealed a significant pattern of bidirectional (closed-loop) connectivity linking the right posterior cerebellum with bilateral temporo-parietal junction (TPJ), associated with behavior understanding. These connections are consistent with known anatomical data on closed loops between the cerebellum and cerebrum, although contralateral closed loops typically dominate. This analysis improves on an earlier psychophysiological interaction analysis of this dataset, which had failed to reveal such evidence of closed loops. Within the cerebrum, there were connections between the bilateral areas of TPJ, as well as connections between bilateral TPJ and the (ventral and dorsal) medial prefrontal cortex. The discussion centers on the function of cerebro-cerebellar connections in generating internal cerebellar "forward" models, potentially serving the automatic understanding, prediction, and error correction of behavioral sequences.

Oral and written picture description in individuals with aphasia.

BACKGROUND: Aphasia is characterized by difficulties in connected speech/writing. AIMS: To explore the differences between the oral and written description of a picture in individuals with chronic aphasia (IWA) and healthy controls. Descriptions were controlled for productivity, efficiency, grammatical organization, substitution behaviour and discourse organization. METHODS & PROCEDURES: Fifty IWA and 50 healthy controls matched for age, gender and education provided an oral and written description of a black-and-white situational drawing from the Dutch version of the Comprehensive Aphasia Test. Between- and within-group analyses were carried out and the reliability of the test instrument was assessed. OUTCOMES & RESULTS: The language samples of the healthy controls were more elaborate, more efficient, syntactically richer, more coherent, and consisted of fewer spoken and written language errors than the samples of the IWA. Within-group comparisons showed that connected writing is more sensitive than connected speech to capture aphasic symptoms. CONCLUSIONS & IMPLICATIONS: The analysis of both modalities (speech and writing) at the discourse level allows one to assess simultaneously micro- and macro-linguistic skills and their potential interrelations in a given IWA. Connected writing appears to be more sensitive in discriminating IWA from healthy controls than connected speech. This method for analyzing language samples should, however, be used in conjunction with other assessment tools.

Cognate effects and cognitive control in patients with parallel and differential bilingual aphasia.

BACKGROUND: Until today, there is no satisfying explanation for why one language may recover worse than another in differential bilingual aphasia. One potential explanation that has been largely unexplored is that differential aphasia is the consequence of a loss of language control rather than a loss of linguistic representations. Language control is part of a general control mechanism that also manages non-linguistic cognitive control. If this system is impaired, patients with differential aphasia could still show bilingual language activation, but they may be unable to manage activation in non-target languages, so that performance in another language is hindered. AIMS: To investigate whether a loss of cognitive control, rather than the loss of word representations in a particular language, might underlie differential aphasia symptoms. METHODS & PROCEDURES: We compared the performance of seven bilinguals with differential and eight bilinguals with parallel aphasia with 19 control bilinguals in a lexical decision and a flanker task to assess bilingual language co-activation and non-linguistic control respectively. OUTCOMES & RESULTS: We found similar cognate effects in the three groups, indicating similar lexical processing across groups. Additionally, we found a larger non-linguistic control congruency effect only for the patients with differential aphasia. CONCLUSIONS & IMPLICATIONS: The present data indicate preserved language co-activation for patients with parallel as well as differential aphasia. Furthermore, the results suggest a general cognitive control dysfunction, specifically for differential aphasia. Taken together, the results of the current study provide further support for the hypothesis of impaired cognitive control abilities in patients with differential aphasia, which has both theoretical and practical implications.

Is the Self-Reporting of Failed Back Surgery Syndrome Patients Treated With Spinal Cord Stimulation in Line With Objective Measurements?

OBJECTIVES: To understand the subjective pain experience of patients, healthcare providers rely heavily on self-reporting. However, to quantify this unique pain experience, objective parameters are not yet available in daily clinical practice. With regard to patients with failed back surgery syndrome (FBSS) treated with spinal cord stimulation (SCS), pain therapists may recover the individual functional information about the patient's posture from the implantable pulse generator (IPG) of the stimulator. The aim of this study is to investigate whether subjective self-reporting is in correlation with the functional capacities of a patient. MATERIALS AND METHODS: Thirty-nine patients with FBSS, treated with SCS were included. The accelerometer in the IPG detects positional changes and provides an objective output of seven functional positions (lying back, lying prone, lying left, lying right, transition, upright, and upright + mobile). The Oswestry Disability Index (ODI), VAS-diary, and the Pittsburgh Sleep Quality Index (PSQI) were assessed to evaluate physical functioning, pain intensities, and subjective sleep quality. Additionally, 21 patients wore a wearable actigraph device to objectify sleep quality. The agreement and Spearman correlations between objective and subjective parameters were assessed. RESULTS: Spearman rank correlations revealed no significant correlations between the ODI (subscales walking, sitting, standing, and sleeping) and the output of the IPG (percentage upright + mobile, transition, upright, and lying, respectively). Sleep parameters measured with the Actiwatch and the PSQI were not in agreement. CONCLUSIONS: This study demonstrated that self-reporting questionnaires do not correlate with the findings of objective measurements. Therefore, we recommend using both subjective and objective parameters when determining treatment options for FBSS patients.

Tell me twice: A multi-study analysis of the functional connectivity between the cerebrum and cerebellum after repeated trait information.

This multi-study analysis (6 fMRI studies; 142 participants) explores the functional activation and connectivity of the cerebellum with the cerebrum during repeated behavioral information uptake informing about personality traits of different persons. The results suggest that trait repetition recruits activity in areas belonging to the mentalizing and executive control networks in the cerebrum, and the executive control areas in the cerebellum. Cerebral activation was observed in the executive control network including the posterior medial frontal cortex (pmFC), the bilateral prefrontal cortex (PFC) and bilateral inferior parietal cortex (IPC), in the mentalizing network including the bilateral middle temporal cortex (MTC) extending to the right superior temporal cortex (STC), as well as in the visual network including the left cuneus (Cun) and the left inferior occipital cortex. Moreover, cerebellar activation was found bilaterally in lobules VI and VII belonging to the executive control network. Importantly, significant patterns of functional connectivity were found linking these cerebellar executive areas with cerebral executive areas in the medial pmFC, the left PFC and the left IPC, and mentalizing areas in the left MTC. In addition, connectivity was found between the cerebral areas in the left hemisphere involved in the executive and mentalizing networks, as well as with their homolog areas in the right hemisphere. The discussion centers on the role of these cerebello-cerebral connections in matching internal predictions generated by the cerebellum with external information from the cerebrum, presumably involving the sequencing of behaviors.

Targeting the Cerebellum by Noninvasive Neurostimulation: a Review.

Transcranial magnetic and electric stimulation of the brain are novel and highly promising techniques currently employed in both research and clinical practice. Improving or rehabilitating brain functions by modulating excitability with these noninvasive tools is an exciting new area in neuroscience. Since the cerebellum is closely connected with the cerebral regions subserving motor, associative, and affective functions, the cerebello-thalamo-cortical pathways are an interesting target for these new techniques. Targeting the cerebellum represents a novel way to modulate the excitability of remote cortical regions and their functions. This review brings together the studies that have applied cerebellar stimulation, magnetic and electric, and presents an overview of the current knowledge and unsolved issues. Some recommendations for future research are implemented as well.

The Posterior Fossa and Foreign Accent Syndrome: Report of Two New Cases and Review of the Literature.

Foreign accent syndrome is a rare motor speech disorder that causes patients to speak their language with a non-native accent. In the neurogenic condition, the disorder develops after lesions in the language dominant hemisphere, often affecting Broca's area, the insula, the supplementary motor area and the primary motor cortex. Here, we present two new cases of FAS after posterior fossa lesions. The first case is a 44-year-old, right-handed, Dutch-speaking man who suffered motor speech disturbances and a left hemiplegia after a pontine infarction. Quantified SPECT showed a bilateral hypoperfusion in the inferior lateral prefrontal and medial inferior frontal regions as well as a significant left cerebellar hypoperfusion. Further clinical investigations led to an additional diagnosis of brainstem cognitive affective syndrome which closely relates to Schmahmann's syndrome. The second patient was a 72-year-old right-handed polyglot English man who suffered a stroke in the vascular territory of the left posterior inferior cerebellar artery (PICA) and developed a foreign accent in his mother tongue (English) and in a later learnt language (Dutch). In this paper, we discuss how the occurrence of this peculiar motor speech disorder can be related to a lesion affecting the posterior fossa structures.

Twiddler's Syndrome and Neuromodulation-Devices: A Troubled Marriage.

OBJECTIVE: The occurrence of Twiddler's syndrome in subjects with neurostimulator devices is poorly understood and might be influenced by age, sex, BMI, use of medication or psychologic disorders. METHODS: Two hundred thiry-five patients who received a neuromodulator were included in this retrospective study in a period between 2008 and 2015. The subjects were divided into a group of Twiddler's syndrome patients (TS) and a group of non-Twiddler's patients (NTS). Outcome measures were gender, age at implantation, type of neuromodulation, use of antipsychotics, antidepressants and opioids, the presence of other psychologic disorders and BMI. RESULTS: Both groups differ significantly in age (p = 0.024), weight (p = 0.001) and BMI (p = 0.001). No statistical difference was found in the type of neuromodulation (p = 0.537), gender (p = 0.368), the use of antipsychotics (p = 0.071), antidepressants (p = 0.097), and opioids (p = 1). Forward stepwise logistic regression of all variables showed that age of implementation (p = 0.029), the use of antipsychotics (p = 0.022) and BMI (p = 0.001) were statistically significant for predicting Twiddler's syndrome. CONCLUSION: Twiddler's syndrome is an uncommon complication of neuromodulation implantable devices. Younger age, use of antipsychotics, and high BMI are risk factors that can be used to facilitate rapid diagnosis and treatment.

Functional connectivity between the cerebrum and cerebellum in social cognition: A multi-study analysis.

This multi-study connectivity analysis explores the functional connectivity of the cerebellum with the cerebrum in social mentalizing, that is, understanding the mind of another person. The analysis covers 5 studies (n=92) involving abstract and complex forms of social mentalizing such as (a) person and group impression formation based on behavioral descriptions and (b) constructing personal counterfactual events (i.e., how the past could have turned out better). The results suggest that cerebellar activity during these social processes reflects a domain-specific mentalizing functionality that is strongly connected with a corresponding mentalizing network in the cerebrum. A significant pattern of connectivity was found linking the dorsal medial prefrontal cortex (mPFC) and the right temporo-parietal junction (TPJ) with the right posterior cerebellum, and linking the latter with the left TPJ. In addition, in the cerebrum, further connectivity was found through links of the bilateral TPJ with the dorsal mPFC, orbitofrontal cortex and between right and left TPJ. The discussion centers on the role of these cerebro-cerebellar connections in matching external information from the cerebrum with internal predictions generated by the cerebellum. These internal predictions might involve the sequencing of the person's behaviors.

Cerebellum: from Fundamentals to Translational Approaches. The Seventh International Symposium of the Society for Research on the Cerebellum.

In terms of cerebellar research and ataxiology, a most fascinating period is currently going on. Numerous academic groups are now focusing their innovative research on the so-called little brain, hidden at the bottom of our brain. Indeed, its unique anatomical features make the cerebellum a wonderful window to address major questions about the central nervous system. The seventh international symposium of the SRC was held in Brussels at the Palace of Academies from May 8 to 10, 2015. The main goal of this dense symposium was to gather in a 2-day meeting senior researchers of exceptional scientific quality and talented junior scientists from all over the world working in the multidisciplinary field of cerebellar research. Fundamental and clinical researchers shared the latest knowledge and developments in this rapidly growing field. New ideas, addressed in a variety of inspiring talks, provoked a vivid debate. Advances in genetics, development, electrophysiology, neuroimaging, neurocognition and affect, as well as in the cerebellar ataxias and the controversies on the roles and functions of the cerebellum were presented. The Ferdinando Rossi lecture and the key-note lecture were delivered by Jan Voogd and Chris De Zeeuw, respectively. Contacts between researchers of different neuroscientific disciplines established a robust basis for novel trends and promising new cooperations between researchers and their centers spread all over the world.

Consensus Paper: Revisiting the Symptoms and Signs of Cerebellar Syndrome.

The cerebellum is involved in sensorimotor operations, cognitive tasks and affective processes. Here, we revisit the concept of the cerebellar syndrome in the light of recent advances in our understanding of cerebellar operations. The key symptoms and signs of cerebellar dysfunction, often grouped under the generic term of ataxia, are discussed. Vertigo, dizziness, and imbalance are associated with lesions of the vestibulo-cerebellar, vestibulo-spinal, or cerebellar ocular motor systems. The cerebellum plays a major role in the online to long-term control of eye movements (control of calibration, reduction of eye instability, maintenance of ocular alignment). Ocular instability, nystagmus, saccadic intrusions, impaired smooth pursuit, impaired vestibulo-ocular reflex (VOR), and ocular misalignment are at the core of oculomotor cerebellar deficits. As a motor speech disorder, ataxic dysarthria is highly suggestive of cerebellar pathology. Regarding motor control of limbs, hypotonia, a- or dysdiadochokinesia, dysmetria, grasping deficits and various tremor phenomenologies are observed in cerebellar disorders to varying degrees. There is clear evidence that the cerebellum participates in force perception and proprioceptive sense during active movements. Gait is staggering with a wide base, and tandem gait is very often impaired in cerebellar disorders. In terms of cognitive and affective operations, impairments are found in executive functions, visual-spatial processing, linguistic function, and affective regulation (Schmahmann's syndrome). Nonmotor linguistic deficits including disruption of articulatory and graphomotor planning, language dynamics, verbal fluency, phonological, and semantic word retrieval, expressive and receptive syntax, and various aspects of reading and writing may be impaired after cerebellar damage. The cerebellum is organized into (a) a primary sensorimotor region in the anterior lobe and adjacent part of lobule VI, (b) a second sensorimotor region in lobule VIII, and (c) cognitive and limbic regions located in the posterior lobe (lobule VI, lobule VIIA which includes crus I and crus II, and lobule VIIB). The limbic cerebellum is mainly represented in the posterior vermis. The cortico-ponto-cerebellar and cerebello-thalamo-cortical loops establish close functional connections between the cerebellum and the supratentorial motor, paralimbic and association cortices, and cerebellar symptoms are associated with a disruption of these loops.

The CAM test: a novel tool to quantify the decline in vertical upper limb pointing movements with ageing.

BACKGROUND AND AIM: Although upper limb movements in the vertical plane are very commonly used during the activities of daily life, there is still a lack of a reliable and easy standardized procedure to quantify them. In particular, ageing is associated with a decline in performances of coordinated movements, but a tool to quantify this decline is missing. METHODS: We created a novel portable test called counting arm movement test (CAM test). Participants were asked to perform fast and accurate successive pointing movements towards two fixed targets (mechanical counters) located in a vertical plane in the parasagittal axis during three different time periods (15, 30, 45 s). Each upper limb was assessed separately. The test was evaluated in a group of 63 healthy subjects (mean age ± SD 49.1 ± 19.8 years; F/M 33/30; range 18-87 years). RESULTS: Motor performances (number of clicks) significantly decreased as a function of age for both the dominant side (age effect; linear regression; p < 0.0001 for 15, 30 and 45 s) and the non-dominant side (linear regression; p < 0.0001 for 15, 30 and 45 s). Performances on the dominant and non-dominant side were linearly correlated with the time periods (p < 0.0001 on both sides). The symmetry index (ratio of performance on the dominant side divided by performance on the non-dominant side) was correlated linearly and positively with the duration of the test (y = 0.002x + 1.053; p = 0.0056). We also found a linear relationship between upper limb length and motor performance on the non-dominant side for 15 s (p = 0.023) and 45 s (p = 0.041). The test was characterized by a very high correlation between the results obtained by two investigators during two successive sessions in a subgroup of 7 subjects (Pearson product moment correlation: 0.989 for the dominant side and 0.988 for the non-dominant side). CONCLUSION: The CAM test appears as a robust and low cost tool to quantify upper limb pointing movements. In particular, the test strongly discriminates the effects of age upon motor performances in upper limbs. Future studies are now required to establish the sensitivity, specificity and reliability of this procedure in selected neuromuscular or skeletal diseases affecting the elderly.

Social cognition and the cerebellum: A meta-analytic connectivity analysis.

This meta-analytic connectivity modeling (MACM) study explores the functional connectivity of the cerebellum with the cerebrum in social cognitive processes. In a recent meta-analysis, Van Overwalle, Baetens, Mariën, and Vandekerckhove (2014) documented that the cerebellum is implicated in social processes of "body" reading (mirroring; e.g., understanding other persons' intentions from observing their movements) and "mind" reading (mentalizing, e.g., inferring other persons' beliefs, intentions or personality traits, reconstructing persons' past, future, or hypothetical events). In a recent functional connectivity study, Buckner et al. (2011) offered a novel parcellation of cerebellar topography that substantially overlaps with the cerebellar meta-analytic findings of Van Overwalle et al. (2014). This overlap suggests that the involvement of the cerebellum in social reasoning depends on its functional connectivity with the cerebrum. To test this hypothesis, we explored the meta-analytic co-activations as indices of functional connectivity between the cerebellum and the cerebrum during social cognition. The MACM results confirm substantial and distinct connectivity with respect to the functions of (a) action understanding ("body" reading) and (b) mentalizing ("mind" reading). The consistent and strong connectivity findings of this analysis suggest that cerebellar activity during social judgments reflects distinct mirroring and mentalizing functionality, and that these cerebellar functions are connected with corresponding functional networks in the cerebrum.

Cognitive and affective disturbances following focal brainstem lesions: a review and report of three cases.

Although insights in cerebellar neurocognition and affect are continuously growing, little is known about the role of the brainstem in cognitive and behavioural processing. In this paper, it is hypothesized that the brainstem is an inherent functional part of the cerebellocerebral network subserving cognition and affect, and that isolated brainstem damage may cause a constellation of symptoms closely resembling the cerebellar cognitive affective syndrome (CCAS) following cerebellar pathology. In order to investigate these premises, the available literature on cognitive and affective disturbances following brainstem lesions was critically reviewed starting from the pioneer descriptions in the 1950s till June 2012. Three personal cases were added to a study group of 75 cases with isolated vascular brainstem damage. In a cohort of 30 patients that allowed construction of anatomoclinical correlations in a reliable way, a range of cognitive and behavioural symptoms, typically associated with impairment of cortical or limbic areas, were identified. Executive dysfunction, attentional deficits and a decline in general intellectual capacity represent the most common cognitive findings, but memory, visuospatial skills, language and praxis may be impaired as well. Almost half of the cases presented with behavioural or affective changes. Analysis of SPECT findings indicates that functional suppression of frontal, parietal and to a lesser extent also the temporal areas are common phenomena after isolated brainstem stroke. As reflected by diaschisis affecting the cerebellocerebral network, a loss of excitatory input from the brainstem to the cerebellum and cerebrum may induce disruption of several cortical regions as well as emotional control centres resulting in and a constellation of symptoms closely resembling the CCAS. The pathophysiological mechanism underlying brainstem-induced cognitive and affective disturbances is discussed.

Cerebellum and apraxia.

As early as the beginning of the nineteenth century, a variety of nonmotor cognitive and affective impairments associated with cerebellar pathology were occasionally documented. A causal link between cerebellar disease and nonmotor cognitive and affective disorders has, however, been dismissed for almost two centuries. During the past decades, the prevailing view of the cerebellum as a mere coordinator of autonomic and somatic motor function has changed fundamentally. Substantial progress has been made in elucidating the neuroanatomical connections of the cerebellum with the supratentorial association cortices that subserve nonmotor cognition and affect. Furthermore, functional neuroimaging studies and neurophysiological and neuropsychological research have shown that the cerebellum is crucially involved in modulating cognitive and affective processes. This paper presents an overview of the clinical and neuroradiological evidence supporting the view that the cerebellum plays an intrinsic part in purposeful, skilled motor actions. Despite the increasing number of studies devoted to a further refinement of the typology and anatomoclinical configurations of apraxia related to cerebellar pathology, the exact underlying pathophysiological mechanisms of cerebellar involvement remain to be elucidated. As genuine planning, organization, and execution disorders of skilled motor actions not due to motor, sensory, or general intellectual failure, the apraxias following disruption of the cerebrocerebellar network may be hypothetically considered to form part of the executive cluster of the cerebellar cognitive affective syndrome (CCAS), a highly influential concept defined by Schmahmann and Sherman (Brain 121:561-579, 1998) on the basis of four symptom clusters grouping related neurocognitive and affective deficits (executive, visuospatial, affective, and linguistic impairments). However, since only a handful of studies have explored the possible role of the cerebellum in apraxic disorders, the pathophysiological mechanisms subserving cerebellar-induced apraxia remain to be elucidated.

Apraxic agraphia following bithalamic damage.

OBJECTIVES: Apraxic agraphia (AA) is a peripheral writing disorder generally considered to result from a causative lesion in the parietal and/or prefrontal lobe of the language dominant hemisphere (De Smet, Engelborghs, Paquier, De Deyn, & Mariën, 2011). De Smet et al. (2011), however, confirmed that AA might be associated with lesions outside the typical language areas such as the cerebellum or the thalamus. We report a 32-year-old ambidextrous patient with a left frontal lobectomy who following bilateral thalamic damage developed AA. METHOD: Detailed neurolinguistic and neurocognitive test results were obtained after resection of an extensive left frontal lobe tumour by means of a set of standardised tests. Repeated investigations were performed after a bithalamic stroke. Functional imaging was performed by means of quantified SPECT. RESULTS: Normal neurolinguistic test results were obtained after tumour resection. Neurocognitive test results, however, showed a dysexecutive syndrome and frontal behavioural deficits, including response inhibition. AA occurred after a bithalamic stroke while non-handwriting written language skills, such as typing, were normal. Quantified SPECT showed a significant bifrontal hypoperfusion. CONCLUSION: Neurolinguistic follow-up findings and SPECT evidence in this unique patient with bithalamic damage for the first time indicate that AA in the alphabetic script may result from diaschisis affecting the frontal writing centre. The findings suggest that the thalamus is critically implicated in the neural network subserving graphomotor processing.

Psychosis associated behavioral and psychological signs and symptoms in mild cognitive impairment and Alzheimer's dementia.

OBJECTIVES: The aim of this study is to determine the prevalence of psychosis in mild cognitive impairment (MCI, Petersen's criteria) and patients with Alzheimer's dementia, and to characterize the associated behavioral and psychological signs and symptoms of dementia (BPSD). METHOD: A cross-sectional analysis of baseline data from an ongoing, prospective, longitudinal study on BPSD was performed, including 270 MCI and 402 AD patients. BPSD assessment was performed through Middelheim Frontality Score (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory (CMAI) and Cornell Scale for Depression in Dementia (CSDD). Psychosis was considered to be clinically relevant when delusions and/or hallucinations occurred at least once in the last two weeks prior to the BPSD assessment. RESULTS: The prevalence of psychosis in AD (40%) was higher than in MCI (14%; p < 0.001). AD patients with psychosis showed more severe frontal lobe, BPSD, agitation and depressive symptoms (MFS, Behave-AD, CMAI and CSDD total scores), whereas MCI patients with psychosis only showed more severe frontal lobe and physically non-aggressive agitated behavior. In addition, only in psychotic AD patients, all BPSD and types of agitation were more severe compared to non-psychotic AD patients. Comparing MCI and AD patients, MCI patients with psychosis did not show more severe frontal lobe, behavioral and psychological (Behave-AD), depressive symptoms or agitation than AD patients without psychosis. CONCLUSION: AD patients clearly display psychosis associated BPSD, whereas MCI patients only display more severe frontal lobe symptoms and physically non-aggressive agitated behavior, but also less pronounced than in AD.

Agitation-associated behavioral symptoms in mild cognitive impairment and Alzheimer's dementia.

OBJECTIVES: The aim of this study is to determine the prevalence of agitation in mild cognitive impairment (MCI, Petersen's criteria) and patients with Alzheimer's dementia (AD), and to characterize the associated behavioral symptoms. METHOD: A cross-sectional analysis of baseline data from a prospective, longitudinal study on behavioral symptoms was performed, including 268 MCI and 393 AD patients. Behavioral assessment was performed through Middelheim Frontality Score (MFS), Behavioral Pathology in Alzheimer's Disease Rating Scale (Behave-AD) and Cornell Scale for Depression in Dementia (CSDD). Agitated behavior was considered to be clinically relevant when one or more items of the Cohen-Mansfield Agitation Inventory (CMAI) occurred at least once a week. RESULTS: The prevalence of agitation in AD (76%) was higher than in MCI (60%; p < 0.001). Patients with agitation showed more severe frontal lobe, behavioral and depressive symptoms (MFS, Behave-AD and CSDD total scores). In agitated AD patients, all behavioral symptoms and types of agitation were more severe compared to non-agitated AD patients, but in agitated MCI patients only for diurnal rhythm disturbances. This resulted in more severe Behave-AD global scores in patients with agitation as compared to patients without agitation. Comparing MCI and AD patients, MCI patients with agitation showed more severe behavioral and depressive symptoms than AD patients without agitation. The structure of agitation in AD consisted of more aggressive and physically non-aggressive behavior than in MCI. CONCLUSION: Frontal lobe, behavioral and depressive symptoms are more severe in MCI and AD patients with clinically relevant agitation as compared to patients without agitation. However, this association is less pronounced in MCI.

Social cognition and the cerebellum: a meta-analysis of over 350 fMRI studies.

This meta-analysis explores the role of the cerebellum in social cognition. Recent meta-analyses of neuroimaging studies since 2008 demonstrate that the cerebellum is only marginally involved in social cognition and emotionality, with a few meta-analyses pointing to an involvement of at most 54% of the individual studies. In this study, novel meta-analyses of over 350 fMRI studies, dividing up the domain of social cognition in homogeneous subdomains, confirmed this low involvement of the cerebellum in conditions that trigger the mirror network (e.g., when familiar movements of body parts are observed) and the mentalizing network (when no moving body parts or unfamiliar movements are present). There is, however, one set of mentalizing conditions that strongly involve the cerebellum in 50-100% of the individual studies. In particular, when the level of abstraction is high, such as when behaviors are described in terms of traits or permanent characteristics, in terms of groups rather than individuals, in terms of the past (episodic autobiographic memory) or the future rather than the present, or in terms of hypothetical events that may happen. An activation likelihood estimation (ALE) meta-analysis conducted in this study reveals that the cerebellum is critically implicated in social cognition and that the areas of the cerebellum which are consistently involved in social cognitive processes show extensive overlap with the areas involved in sensorimotor (during mirror and self-judgments tasks) as well as in executive functioning (across all tasks). We discuss the role of the cerebellum in social cognition in general and in higher abstraction mentalizing in particular. We also point out a number of methodological limitations of some available studies on the social brain that hamper the detection of cerebellar activity.