Neuropsychiatric symptoms in 921 elderly subjects with dementia: a comparison between vascular and neurodegenerative types.

OBJECTIVE: i) to describe the neuropsychiatric profile of elderly subjects with dementia by comparing vascular (VaD) and degenerative dementias, i.e. dementia with Lewy bodies (DLB) and Alzheimer's disease (AD); ii) to assess whether the severity and type of dementia are associated with clinically relevant neuropsychiatric symptoms (CR-NPS). METHOD: One hundred and thirty-one out-patients with VaD, 100 with DLB and 690 with AD were studied. NPS were evaluated by the neuropsychiatric inventory (NPI). RESULTS: Vascular dementia had lower total and domain-specific NPI scores and a lower frequency of CR-NPS than AD and DLB, for which frequency of CR-NPS increased significantly with disease severity, particularly in AD. Logistic regression analysis showed that a higher CDR score and a diagnosis of degenerative dementia were independently associated with CR-NPS. CONCLUSION: Vascular dementia is associated less with CR-NPS than AD and DLB. Frequency of CR-NPS increases with disease severity in AD and, to a lesser extent, in DLB.

Effects of levodopa oral bolus on the kinematics of the pointing movements in Parkinson's disease patients.

We studied the time-course of a levodopa oral bolus effects on the kinematics of patients affected by a mild akinetic-rigid form of idiopathic Parkinson's disease (PD). Eleven PD patients were evaluated: a) in OFF-state, that is before their first medication or after its withdrawal, b) in ON-state, that is at 1/2, 1, 2, 3, 4, 5, 6, 24, 30 and 48 hours after the administration of 250 mg of levodopa plus 25mg of carbidopa. The main kinematics (i. e.movement time, peak of velocity, peak of acceleration and peak of deceleration) of pointing movements to six target-stimuli placed on the horizontal plane of a table were recorded. Clinical conditions were assessed according to the Motor Examination section of the Unified Parkinson's Disease Rating Scale. The levopoda bolus had stable clinical effects only within the first six hours from its administration. The decline of the clinical response was marked by the changes of peak acceleration whereas other kinematics (i. e. movement time and the peak of velocity) changed also in the late observations (24, 30 and 48 hours after drug intake). The dissociation between the persistent improvement on movement time on peak velocity and the rapid deterioration of levodopa effects on early kinematics (i. e. peak acceleration) could be accounted for by a progressive decline in movement programming.

Corticocortical connections of area F3 (SMA-proper) and area F6 (pre-SMA) in the macaque monkey.

The monkey mesial area 6 comprises two distinct cytoarchitectonic areas: F3 [supplementary motor area properly defined (SMA-proper)], located caudally, and F6 (pre-SMA), located rostrally. The aim of the present study was to describe the corticocortical connections of these two areas. To this purpose restricted injections of neuronal tracers (wheat germ-agglutinin conjugated to horseradish peroxidase, fluorescent tracers) were made in different somatotopic fields of F3, F6, and F1 (area 4) and their transport plotted. The results showed that F3 and F6 differ markedly in their cortical connections. F3 is richly linked with F1 and the posterior premotor and cingulate areas (F2, F4, 24d). Connections with the anterior premotor and cingulate areas (F6, F7, F5, 24c) although present, are relatively modest. There is no input from the prefrontal lobe. F3 is also connected with several postrolandic cortical areas. These connections are with areas PC, PE, and PEa in the superior parietal lobule, cingulate areas 23 and PEci, the opercular parietal areas (PFop, PGop, SII) and the granular insula. F6 receives a rich input from the anterior premotor areas (especially F5) and cingulate area 24c, whereas its input from the posterior premotor and cingulate areas is very weak. A strong input originates from area 46. There are no connections with F1. The connections with the postrolandic areas are extremely meagre. They are with areas PG and PFG in the inferior parietal lobule, the disgranular insula, and the superior temporal sulcus. A further result was the demonstration of a differential connectivity pattern of the cingulate areas 24d and 24c. Area 24d is strongly linked with F1 and F3, whereas area 24c is connected mostly with F6. The present data support the notion that the classical SMA comprises two functionally distinct areas. They suggest that F6 (the rostral area) is responsible for the "SMA" so-called high level motor functions, whereas F3 (the caudal area) is more closely related to movement execution.

Afferent and efferent projections of the inferior area 6 in the macaque monkey.

The rostral part of the agranular frontal cortex (area 6) can be subdivided on the basis of its cytoarchitecture, enzymatic properties, and connections into two large sectors: a superior region, lying medial to the spur of the arcuate sulcus, and an inferior region, lying lateral to it. In this study we traced the afferent and efferent connections of the inferior region of area 6 by injecting small amounts of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) and fluorescent tracers (fast blue and diamidino yellow) into restricted parts of inferior area 6 and in physiologically determined fields of area 4. There is an ordered topographic pattern of connections between inferior area 6 and area 4. The region near the spur of the arcuate sulcus (hand field) projects to the area 4 hand field while the lateral part of inferior area 6 (mouth field) is connected with the corresponding field in area 4. The organization of the connections between the two fields is, however, different. The hand fields in area 6 and 4 have direct reciprocal projections, whereas the mouth field in the postarcuate cortex relays information to area 4 via a zone intermediate between the arcuate and the central sulcus. This zone corresponds to the cytochrome oxidase area F4 (Matelli, Luppino, and Rizzolatti: Behav. Brain Res. 18: 125-137, '85). The inferior area 6 also has topographically organized connections with the supplementary motor area. The inferior area 6 receives and sends fibers to a series of discrete cortical areas located in the lower cortical moiety (Sanides: The Structure and Function of the Nervous Tissue, Vol. 5. New York: Academic Press, pp 329-453, '72). These areas that form a broad ring around the central sulcus are the ventral bank of the principal sulcus and the adjacent area 46, the precentral operculum (PrOC), area SII (Jones and Burton: J. Comp. Neurol. 168:197-248, '76), the parietal operculum, and the rostral part of the inferior parietal lobule including the lower bank of the intraparietal sulcus. Finally, the inferior area 6 has sparse but consistent connections with insular and cingulate cortices. The functional significance of this complex pattern of connections is discussed.

The effect of hemidecortication on the inhibitory interactions in the superior colliculus of the cat.

Single neurons were recorded extracellularly from the superficial layers of the superior colliculus (SC) in 21 curarized cats. Four animals were normal unoperated cats, 17 were animals in which all cortical visual areas were ablated on one side from 7 to 69 days before the electrophysiological experiments. After cortical ablation all animals were blind in the visual field contralateral to the ablated side. In both normal and hemianopsic cats the effect of a visual stimulus located very far from the excitatory part of the unit receptive field, on the neuron responses to visual stimuli was studied. The remote stimulus (extra-field stimulus) was a hand moved black spot 10 degrees in diameter. In normal animals the introduction of the extra-field stimulus in the hemifield contralateral or ipsilateral to the recorded SC produced a marked reduction of unit responses to visual stimuli presented in their receptive field. This effect was particularly strong when the extra-field stimuli were introduced in the hemifield contralateral to the recorded side. In the hemianopsic animals the neurons of the SC ipsilateral to the lesion (receptive fields in the behaviorally blind hemifield) responded well to visual stimuli, but were only weakly inhibited by the extra-field stimuli presented in the blind hemifield. The neurons of this colliculus with the exception of those in the upper part of stratum griseum superficiale were normally inhibited by stimuli presented in the normal hemifield. The neurons of the SC contralateral to the lesion responded well to visual stimuli and were normally inhibited by stimuli presented in the normal hemifield; they were virtually not affected by stimuli presented in the blind hemifield. Mechanisms responsible for the abnormal inhibitory interactions between and within colliculi after cortical lesions and the possible behavioral implications of the findings are discussed.

Multiple representations of body movements in mesial area 6 and the adjacent cingulate cortex: an intracortical microstimulation study in the macaque monkey.

The mesial agranular frontal cortex that lies rostral to area 4 (F1) is formed by two distinct cytoarchitectonic areas: F3, located caudally, and F6, located rostrally. In the present experiments we investigated the organization of F3 and F6 by observing the motor responses evoked by their intracortical electrical microstimulation. Our main purpose was to find out whether the cytoarchitectonic subdivision of the mesial agranular frontal cortex into two areas has a physiological counterpart. The result showed that F3 (the caudal area) contains a complete motor representation with hindlimb movements located caudally, forelimb movements located centrally, and orofacial movements located rostrally. The great majority of limb movements involved proximal joints. With respect to F1, F3 showed the following functional characteristics: (1) lack of segregation between proximal and distal movements, (2) larger percentage of complex movements, and (3) higher excitability threshold. Movements were more difficult to elicit from F6 (the rostral area) than from F3. However, by using a longer stimulus train duration (100 ms) 39.3% of tested sites produced body movements. This percentage increased (50.5%) when the electrical stimulation was applied during monkey natural movements instead of when the monkey was still in its chair. Most of the evoked movements concerned the forelimb. More rarely, neck and upper face movements were observed. Unlike F1 and F3 where most movements were fast, slow movements were frequently observed with stimulation of F6. Many of them mimicked natural movements of the animal. Eye movements were evoked from F7 (superior area 6) but not from F6. An additional motor representation was found in the dorsocaudal part of area 24 (24d). This area is topographically organized with a forelimb representation located caudally and ventrally and a hindlimb representation located rostrally and dorsally. The excitability threshold of area 24d is higher than that of F1 and F3. Evoked movements were occasionally observed also after stimulation of area 24c. In conclusion, on the mesial cortical wall rostral to F1, there are at least three independent motor representations. On the basis of somatotopic organization and excitability properties, we propose that the term supplementary motor area (SMA-proper) should be reserved to F3.

Transient topographical amnesia and cingulate cortex damage: a case report.

Transient topographical amnesia (TTA) is the temporary inability to find one's way in familiar or unfamiliar surroundings due to the inability to use well known environmental landmarks for route finding. The syndrome has not been described as having any obvious aetiology and has been thought to be caused by a vascular deficit in right hemispheric structures which are crucial for topographic recognition, i.e. parietal association and parahippocampal cortex. The patient described in the present study complained of several critical episodes of TTA and tonic rigidity of the left limbs. Neuropsychological assessment was normal except for a deficit in spatial memory tasks. Magnetic resonance (MR) imaging of the brain showed an angioma at the border of areas 24d and 23 of the right cingulate cortex. Because area 23 is strategically located in a network that links the parietal associative (area 7a) and parahippocampal cortices, and because these cortical areas are involved in topographical orienting processes, we suggest that a transient functional inactivation of the network caused by epileptic discharges spreading from the damaged cingulate cortex towards the parahippocampal and parietal association cortex could account for the spatial disorder. Similar discharges spreading from area 24d towards the primary motor cortex and/or the spinal cord could account for the episodes of tonic rigidity of the left limbs.

Corticospinal projections from mesial frontal and cingulate areas in the monkey.

We injected neural tracers into the lateral funiculus of the spinal cord in order to relate the sites of origin of the spinal projections from the mesial cortical surface with the cytoarchitectonic organization of this region. We found a close correlation between the origin sites and density of corticospinal projections and the areal organization. The areas most densely labelled were F3 (SMA-proper) and area 24d, whereas F6 (pre-SMA) and area 24c showed a low density of labelling. The segmental topography of the corticospinal projections fitted well with the somatotopy of the mesial cortical areas. We conclude that in the agranular mesial cortex there are four independent motor representations: F3 and 24d where the whole body is represented, and F6 and 24c which are mostly related to arm movements.

Visual receptive fields in the lateral suprasylvian area (Clare-Bishop area) of the cat.

Single units were recorded from the visual area of the lateral suprasylvian gyrus (LSSA or Clare-Bishop area) in 20 unanesthetized cats. Most LSSA units were poorly responsive to stationary visual stimuli, but they responded vigorously to moving visual stimuli. Their receptive fields appeared to be constituted of a large activating region (discharge area) often surrounded by inhibitory flanks. Relating unit behavior to changes of stimulus length, the LSSA neurons could be subdivided into 5 categories. The first category (22 out of 95 units tested, 23.16%) consisted of units showing summation inside the discharge area. Expanding the stimulus outside the discharge area did not affect the response. The second category (7.37%) was formed by units which showed summation inside the discharge area and inhibition when the stimulus was extended outside the discharge area. The third category (21.05%) consisted of units largely insensitive to the stimulus length inside the discharge area, but surrounded by inhibitory flanks. The fourth category (41.05%) consisted of units which showed inhibition of the response when the stimulus, well inside the discharge area, became longer than a certain optimal lenght. They were surrounded by inhibitory flanks. The fifth category (7.37%) was formed by units insensitive to variations of the stimulus length inside as well as outside the discharge area. Almost all units, independent of their category, were directionally specific, that is their response could be decreased 50% or more by varying the direction of movement away from that which gave the maximal response (preferred direction). Typically the response was halved when the stimulus was moved +/- 50 degrees from the preferred direction. Among the directionally specific units, 71% showed the minimal response 180 degrees away from the preferred direction (direction specificity curve type 1), 20% had the minimal response 90 degrees from the preferred direction (direction specificity curve type 2); the remaining could not be classified in this respect. Of LSSA units, 87% (all those of type 1 and many of those of type 2) were directionally selective, that is their response to movement in the preferred direction was at least double that in the opposite direction. The LSSA units usually preferred stimuli moving at rather high speeds. The optimal speed for 71% of units was 20 degrees/sec or greater. Almost all units responded over a wide range of speeds, many of them from 5-10 degrees/sec to over 100 degrees/sec. Most neurons had a low spontaneous activity and some of them remained completely silent for seconds.

Interconnections within the postarcuate cortex (area 6) of the macaque monkey.

Small amounts of horseradish peroxidase conjugated with wheat germ were injected in restricted parts of the postarcuate premotor area of the macaque monkey. It was found that regions of this area having different somatotopic representations are richly interconnected among them. This pattern of intra-areal connectivity was not observed in the precentral motor area. It appears therefore that the postarcuate area is organized according to anatomical principles which are different from those of the primary motor cortex.

Response properties and behavioral modulation of "mouth" neurons of the postarcuate cortex (area 6) in macaque monkeys.

Single neurons were recorded from the "mouth area" of the postarcuate cortex in macaque monkeys. According to their responses to somatosensory stimuli and their activity during the animal's movements, the neurons were subdivided into three classes: (1) neurons activated only by external stimuli; (2) neurons showing an enhancement of their response when a specific motor act followed the external stimulation; (3) neurons responding reliably to external stimuli only if the stimulation triggered a specific, related motor act. Of the recorded neurons, 50% also responded to visual stimuli.

Prevalence and pattern of cognitive impairment in systemic lupus erythematosus patients with and without overt neuropsychiatric manifestations.

The prevalence and pattern of cognitive impairment in systemic lupus erythematosus (SLE) patients with (NPSLE) and without (nSLE) overt neuropsychiatric manifestations were investigated. Fifty-two nSLE patients, 23 NPSLE patients and 27 healthy controls were evaluated with a battery of standardized neuropsychological and psychological tests. Disease duration, disease activity index, and current corticosteroid therapy were collected. Cognitive impairment was identified in 14 (26.9%) and in 12 (52.2%) of subjects with nSLE and NPSLE, respectively. Both SLE groups showed a significant impairment compared with controls on tasks assessing verbal and non-verbal long-term memory, and visuoconstructional abilities. In addition, NPSLE patients reported worse performances than both nSLE patients and controls on task evaluating short-term visuospatial memory. NPSLE subjects were significantly more anxious and depressed compared to both nSLE subjects and controls. By multivariate analysis, only depression levels, among clinical variables, significantly predicted cognitive performance. This study shows that cognitive impairment occurs frequently in both nSLE and NPSLE subjects. The higher frequency in NPSLE may be related to coexisting depressive disturbances.

Interictal executive dysfunction in migraineurs without aura: relationship with duration and intensity of attacks.

Subjects with migraine are at increased risk of subcortical white matter lesions (WML). Reports of cognitive testing in adults with migraine have yielded inconsistent results. We performed a cross-sectional study to assess whether migraine without aura (MwA) is associated with impairment in executive functioning, a typical cognitive correlate of subcortical WML. Forty-five subjects with MwA and 90 controls, matched for age and education, underwent a cognitive battery of tests evaluating executive functions. The following migraine characteristics were collected: age at onset and length of migraine history, and frequency, duration and intensity of attacks. Subjects with MwA performed significantly lower than controls in tests evaluating complex, multifactorial executive functions. After multiple adjustments, the duration and intensity of migraine attacks significantly predicted cognitive disturbances. In the interictal phase of MwA there is evidence of mild executive dysfunction. The cumulative effects of repeated migraine attacks on prefronto-cerebellar loop probably account for our results.