Brain Charts for the Rhesus Macaque Lifespan.

Recent efforts to chart human brain growth across the lifespan using large-scale MRI data have provided reference standards for human brain development. However, similar models for nonhuman primate (NHP) growth are lacking. The rhesus macaque, a widely used NHP in translational neuroscience due to its similarities in brain anatomy, phylogenetics, cognitive, and social behaviors to humans, serves as an ideal NHP model. This study aimed to create normative growth charts for brain structure across the macaque lifespan, enhancing our understanding of neurodevelopment and aging, and facilitating cross-species translational research. Leveraging data from the PRIMatE Data Exchange (PRIME-DE) and other sources, we aggregated 1,522 MRI scans from 1,024 rhesus macaques. We mapped non-linear developmental trajectories for global and regional brain structural changes in volume, cortical thickness, and surface area over the lifespan. Our findings provided normative charts with centile scores for macaque brain structures and revealed key developmental milestones from prenatal stages to aging, highlighting both species-specific and comparable brain maturation patterns between macaques and humans. The charts offer a valuable resource for future NHP studies, particularly those with small sample sizes. Furthermore, the interactive open resource (https://interspeciesmap.childmind.org) supports cross-species comparisons to advance translational neuroscience research.

Brain-computer interaction for online enhancement of visuospatial attention performance.

OBJECTIVE: this study on real-time decoding of visuospatial attention has two objectives: first, to reliably decode self-directed shifts of attention from electroencephalography (EEG) data, and second, to analyze whether this information can be used to enhance visuospatial performance. Visuospatial performance was measured in a target orientation discrimination task, in terms of reaction time, and error rate. APPROACH: Our experiment extends the Posner paradigm by introducing a new type of ambiguous cues to indicate upcoming target location. The cues are designed so that their ambiguity is imperceptible to the user. This entails endogenous shifts of attention which are truly self-directed. Two protocols were implemented to exploit the decoding of attention shifts. The first 'adaptive' protocol uses the decoded locus to display the target. In the second 'warning' protocol, the target position is defined in advance, but a warning is flashed when the target mismatches the decoded locus. MAIN RESULTS: Both protocols were tested in an online experiment involving ten subjects. The reaction time improved in both the adaptive and the warning protocol. The error rate was improved in the adaptive protocol only. SIGNIFICANCE: This proof of concept study brings evidence that visuospatial brain-computer interfaces (BCIs) can be used to enhance improving human-machine interaction in situations where humans must react to off-center events in the visual field.

Simultaneous recording of macaque premotor and primary motor cortex neuronal populations reveals different functional contributions to visuomotor grasp.

To understand the relative contributions of primary motor cortex (M1) and area F5 of the ventral premotor cortex (PMv) to visually guided grasp, we made simultaneous multiple electrode recordings from the hand representations of these two areas in two adult macaque monkeys. The monkeys were trained to fixate, reach out and grasp one of six objects presented in a pseudorandom order. In M1 326 task-related neurons, 104 of which were identified as pyramidal tract neurons, and 138 F5 neurons were analyzed as separate populations. All three populations showed activity that distinguished the six objects grasped by the monkey. These three populations responded in a manner that generalized across different sets of objects. F5 neurons showed object/grasp related tuning earlier than M1 neurons in the visual presentation and premovement periods. Also F5 neurons generally showed a greater preference for particular objects/grasps than did M1 neurons. F5 neurons remained tuned to a particular grasp throughout both the premovement and reach-to-grasp phases of the task, whereas M1 neurons showed different selectivity during the different phases. We also found that different types of grasp appear to be represented by different overall levels of activity within the F5-M1 circuit. Altogether these properties are consistent with the notion that F5 grasping-related neurons play a role in translating visual information about the physical properties of an object into the motor commands that are appropriate for grasping, and which are elaborated within M1 for delivery to the appropriate spinal machinery controlling hand and digit muscles.

A cortico-cortical mechanism mediating object-driven grasp in humans.

Humans and other primates demonstrate an exquisite ability to precisely shape their hand when reaching out to grasp an object. Here we used a recently developed transcranial magnetic stimulation paradigm to examine how information about an object's geometric properties is transformed into specific motor programs. Pairs of transcranial magnetic stimulation pulses were delivered at precise intervals to detect changes in the excitability of cortico-cortical inputs to motor cortex when subjects prepared to grasp different objects. We show that at least 600 ms before movement, there is an enhancement in the excitability of these inputs to the corticospinal neurons projecting from motor cortex to the specific muscles that will be used for the grasp. These changes were object- and muscle-specific, and the degree of modulation in the inputs was correlated with the pattern of muscular activity used later by individual subjects to grasp the objects. In a number of control experiments, we demonstrated that no change in excitability was observed during object presentation alone, under conditions in which subjects imagined grasping the object, or before movements involving the same muscles but without an object. This finding demonstrates a cortico-cortical mechanism subserving the transformation from the geometrical properties of an object to the outputs from motor cortex before grasp that is specific for object-driven movements.

Patterns of muscle activity underlying object-specific grasp by the macaque monkey.

During object grasp, a coordinated activation of distal muscles is required to shape the hand in relation to the physical properties of the object. Despite the fundamental importance of the grasping action, little is known of the muscular activation patterns that allow objects of different sizes and shapes to be grasped. In a study of two adult macaque monkeys, we investigated whether we could distinguish between EMG activation patterns associated with grasp of 12 differently shaped objects, chosen to evoke a wide range of grasping postures. Each object was mounted on a horizontal shuttle held by a weak spring (load force 1-2 N). Objects were located in separate sectors of a "carousel," and inter-trial rotation of the carousel allowed sequential presentation of the objects in pseudorandom order. EMG activity from 10 to 12 digit, hand, and arm muscles was recorded using chronically implanted electrodes. We show that the grasp of different objects was characterized by complex but distinctive patterns of EMG activation. Cluster analysis shows that these object-related EMG patterns were specific and consistent enough to identify the object unequivocally from the EMG recordings alone. EMG-based object identification required a minimum of six EMGs from simultaneously recorded muscles. EMG patterns were consistent across recording sessions in a given monkey but showed some differences between animals. These results identify the specific patterns of activity required to achieve distinct hand postures for grasping, and they open the way to our understanding of how these patterns are generated by the central motor network.

Investigation into non-monosynaptic corticospinal excitation of macaque upper limb single motor units.

There has been considerable recent debate as to relative importance, in the primate, of propriospinal transmission of corticospinal excitation to upper limb motoneurons. Previous studies in the anesthetized macaque monkey suggested that, compared with the cat, the transmission of such excitation via a system of C3-C4 propriospinal neurons may be relatively weak. However, it is possible that in the anesthetized preparation, propriospinal transmission of cortical inputs to motoneurons may be depressed. To address this issue, the current study investigated the responses of single motor units (SMUs) to corticospinal inputs in either awake (n = 1) or lightly sedated (n = 3) macaque monkeys. Recordings in the awake state were made during performance of a precision grip task. The responses of spontaneously discharging SMUs to electrical stimulation of the pyramidal tract (PT) via chronically implanted electrodes were examined for evidence of non-monosynaptic, presumed propriospinal, effects. Single PT stimuli (up to 250 microA; duration, 0.2 ms, 2 Hz) were delivered during steady discharge of the SMU (10-30 imp/s). SMUs were recorded from muscles acting on the thumb (adductor pollicis and abductor pollicis brevis, n = 18), wrist (extensor carpi radialis, n = 29) and elbow (biceps, n = 9). In all SMUs, the poststimulus time histograms to PT stimulation consisted of a single peak at a fixed latency and with a brief duration [0.74 +/- 0.25 (SD) ms, n = 56], consistent with the responses being mediated by monosynaptic action of cortico-motoneuronal (CM) impulses. Later peaks, indicating non-monosynaptic action, were not present even when the probability of the initial peak response was low and when there was no evidence for suppression of ongoing SMU activity following this peak (n = 20 SMUs). Even when repetitive (double-pulse) PT stimuli were used to facilitate transmission through oligosynaptic linkages, no later peaks were observed (16 SMUs). In some thumb muscle SMUs (n = 8), responses to PT stimulation were compared with those evoked by transcranial magnetic stimulation, using a figure-eight coil held over the motor cortex. Responses varied according the orientation of the coil: in the latero-medial position, single peak responses similar to those from the PT were obtained; their latencies confirmed direct excitation of CM cells, and there were no later peaks. In the posterio-anterior orientation, responses had longer latencies and consisted of two to three subpeaks. At least under the conditions that we have tested, the results provide no positive evidence for transmission of cortical excitation to upper limb motoneurons by non-monosynaptic pathways in the macaque monkey.

Activity in ventral and dorsal premotor cortex in response to predictable force-pulse perturbations in a precision grip task.

This study compared the responses of ventral and dorsal premotor cortex (PMv and PMd) neurons to predictable force-pulse perturbations applied during a precision grip. Three monkeys were trained to grasp an unseen instrumented object between the thumb and index finger and to lift and hold it stationary within a position window for 2-2.5 s. The grip and load forces and the object displacement were measured on each trial. Single-unit activity was recorded from the hand regions in the PMv and PMd. In some conditions a predictable perturbation was applied to the object after 1,500 ms of static holding, whereas in other conditions different random combinations of perturbed and unperturbed trials were given. In the perturbed conditions, some were randomly and intermittently presented with a warning flash, whereas some were unsignaled. The activities of 198 cells were modulated during the task performance. Of these cells, 151 were located in the PMv, and 47 were located in the PMd. Although both PMv and PMd neurons had similar discharge patterns, more PMd neurons (84 vs. 43%) showed early pregrip activity. Forty of 106 PMv and 10/30 PMd cells responded to the perturbation with reflexlike triggered reactions. The latency of this response was always <100 ms with a mean of about 55 ms in both the PMv and the PMd. In contrast, 106 PMv and 30 PMd cells tested with the perturbations, only 9 and 10%, respectively, showed significant but nonspecific adaptations to the perturbation. The warning stimulus did not increase the occurrence of specific responses to the perturbation even though 21 of 42 cells related to the grip task also responded to moving visual stimuli. The responses were retinal and frequently involved limited portions of both foveal and peripheral visual fields. When tested with a 75 x 5.5-cm dark bar on a light background, these cells were sensitive to the direction of movement. In summary, the periarcuate premotor area activity to related to predictable force-pulse perturbations seems to reflect a general increase in excitability in contrast to a more specific anticipatory activity such as recorded in the cerebellum. In spite of the strong cerebello-thalamo-cortical projections, the results of the present study suggest that the cortical premotor areas are not involved in the elaboration of adaptive internal models of hand-object dynamics.

The effects of muscimol inactivation of small regions of motor and somatosensory cortex on independent finger movements and force control in the precision grip.

This study investigated the effects of inactivating small regions of the primary somatosensory (SI) and motor (MI) cortex on the control of finger forces in a precision grip. A monkey was trained to grasp and lift a computer-controlled object between the thumb and index finger and to hold it stationary within a narrow position window for 2 s. The grip force applied perpendicular to the object surface, the lifting or load force applied tangentially in the vertical direction, and the vertical displacement were sampled at 100 Hz. Also, the ability of the monkey to extract small pieces of food from narrow wells of a Klüver board was analyzed from video-tape. Preliminary single-unit recordings and microstimulation studies were used to map the extent of the thumb and index-finger representation within SI and MI. Two local injections of 1 microl each (5 microg/microl) of the GABA(A)-agonist muscimol were used to inactivate the thumb and index region of either the pre- or post-central gyrus. The precision grip was differently affected by muscimol injection into either SI or MI. MI injections produced a deficit in the monkey's ability to perform independent finger movements and a general weakness in the finger muscles. Whole-hand grasping movements were inappropriately performed in an attempt to grasp either the instrumented object or morsels of food. Although the effect seemed strongest on intrinsic hand muscles, a clear deficit in digit extension was also noted. As a result, the monkey was unable to lift and maintain the object within the position window for the required 2 s, and, over time, the grip force decreased progressively until the animal stopped working. Following SI injections, the most obvious effect was a loss of finger coordination. In grasping, the placement of the fingers on the object was often abnormal and the monkey seemed unable to control the application of prehensile and lifting forces. However, the detailed analysis of forces revealed that a substantial increase in the grip force occurred well before any deficit in the coordination of finger movements was noted. This observation suggests that cutaneous feedback to SI is essential for the fine control of grip forces.

Neuronal activity in somatosensory cortex of monkeys using a precision grip. I. Receptive fields and discharge patterns.

Three adolescent Macaca fascicularis monkeys weighing between 3.5 and 4 kg were trained to use a precision grip to grasp a metal tab mounted on a low friction vertical track and to lift and hold it in a 12- to 25-mm position window for 1 s. The surface texture of the metal tab in contact with the fingers and the weight of the object could be varied. The activity of 386 single cells with cutaneous receptive fields contacting the metal tab were recorded in Brodmann's areas 3b, 1, 2, 5, and 7 of the somatosensory cortex. In this first of a series of papers, we describe three types of discharge pattern, the receptive-field properties, and the anatomic distribution of the neurons. The majority of the receptive fields were cutaneous and covered less than one digit, and a chi2 test did not reveal any significant differences in the Brodmann's areas representing the thumb and index finger. Two broad categories of discharge pattern cells were identified. The first category, dynamic cells, showed a brief increase in activity beginning near grip onset, which quickly subsided despite continued pressure applied to the receptive field. Some of the dynamic neurons responded to both skin indentation and release. The second category, static cells, had higher activity during the stationary holding phase of the task. These static neurons demonstrated varying degrees of sensitivity to rates of pressure change on the skin. The percentage of dynamic versus static cells was about equal for areas 3b, 2, 5, and 7. Only area 1 had a higher proportion of dynamic cells (76%). A third category was identified that contained cells with significant pregrip activity and included cortical cells with both dynamic or static discharge patterns. Cells in this category showed activity increases before movement in the absence of receptive-field stimulation, suggesting that, in addition to peripheral cutaneous input, these cells also receive strong excitation from movement-related regions of the brain.

Neuronal activity in somatosensory cortex of monkeys using a precision grip. II. Responses To object texture and weights.

Three monkeys were trained to lift and hold a test object within a 12- to 25-mm position window for 1 s. The activity of single neurons was recorded during performance of the task in which both the weight and surface texture of the object were systematically varied. Whenever possible, each cell was tested with three weights (15, 65, and 115 g) and three textures (smooth metal, fine 200 grit sandpaper, and rough 60 grit sandpaper). Of 386 cells recorded in 3 monkeys, 45 cells had cutaneous receptive fields on the index or thumb or part of the thenar eminence and were held long enough to be tested in all 9 combinations of texture and weight. Recordings were made for the entire anterior-posterior extent of the thumb and index finger areas in somatosensory cortex including area 7b. However, the statistical analysis required a selection of only those cells for which nine complete recording conditions were available limiting the sample to cells in areas 2, 5, and 7b. Significant differences in the grip force accompanied 98% of the changes in texture and 78% of the changes in weight. Increasing the object weight also increased the force tangential to the skin surface as measured by the load or lifting force. The peak discharge during lifting was judged to be the most sensitive index of cell activity and was analyzed with a two-way analysis of variance (ANOVA). In addition, peak cell discharge was normalized to allow comparisons among different combinations of texture and weight as well as comparisons among different neurons. Overall, the peak firing frequency of 87% of the cells was significantly modulated by changes in object texture, but changes in object weight affected the peak activity of only 58% of the cells. Almost all (17/18, 94%) of the static cells were influenced by the object texture, and 81% of the dynamic cells that were active only briefly at grip and lift onset were modulated by texture. For some cells, surface texture had a significant effect on neuronal discharge that was independent of the object weight. In contrast, weight-related responses were never simple main effects of the weight alone and appeared instead as significant interactions between texture and weight. Four neurons either increased or decreased activity in a graded fashion with surface structure (roughness) regardless of the object weight (P < 0.05). Ten other neurons showed increases or decreases in response to one or two textures, which might represent either a graded response or a tuning preference for a specific texture. The firing frequency of the majority (31/45) of neurons reflected an interaction of both texture and weight. The cells with texture-related but weight-independent activities were thought to encode surface characteristics that are largely independent of the grip and lifting forces used to manipulate the object. Such constancies could be used to construct internal representations or mental models for planning and controlling object manipulation.

Neuronal activity in somatosensory cortex of monkeys using a precision grip. III. Responses to altered friction perturbations.

The purpose of this investigation was to examine the activity changes in single units of the somatosensory cortex in response to lubricating and adhesive coatings applied to a hand-held object. Three monkeys were trained to grasp an object between the thumb and index fingers and to lift and hold it stationary within a narrow position window for 1 s before release. Grip forces normal to the skin surface, load forces tangential to the skin surface, and the displacement of the object were measured on each trial. Adhesive (rosin) and lubricant (petroleum jelly) coatings were applied to the smooth metal surface of the object to alter the friction against the skin. In addition, neuronal activity evoked by force pulse-perturbations generating shear forces and slip on the skin were compared with the patterns of activity elicited by grasping and lifting the coated surfaces. Following changes in surface coatings, both monkeys modulated the rate at which grip forces normal to the skin surface and load forces tangential to the skin surface were applied during the lifting phase of the task. As a result, the ratio of the rates of change of the two forces was proportionately scaled to the surface coating properties with the more slippery surfaces, having higher ratios. This precise control of normal and tangential forces enabled the monkeys to generate adequate grip forces and prevent slip of the object. From a total of 386 single neurons recorded in the hand area of the somatosensory cortex, 92 were tested with at least 1 coating. Cell discharge changed significantly with changes in surface coating in 62 (67%) of these cells. Of these coating-related cells, 51 were tested with both an adhesive and lubricating coating, and 45 showed significant differences in activity between the untreated metal surface and either the lubricant or the adhesive coating. These cells were divided into three main groups on the basis of their response patterns. In the first group (group A), the peak discharge increased significantly when the grasped surface was covered with lubricant. These cells appeared to be selectively sensitive to slip of the object on the skin. The second group (group B) was less activated by the adhesive surface compared with either the untreated metal or the lubricated surface, and they responded mainly to variations in the force normal to the skin surface. These cells provide useful feedback for the control of grip force. The third group (group C) responded to both slips and to changes in forces tangential to the skin. Most of these cells responded with a biphasic pattern reflecting the bidirectional changes in load force as the object was first accelerated and then decelerated. One hundred sixty-eight of the 386 isolated neurons were tested with brief perturbations during the task. Of these, 147 (88%) responded to the perturbation with a significant change in activity. In most of the cells, the response to the perturbation was shorter than 100 ms with a mean latency of 44.1 +/- 16.3 (SD) ms. For each of the cell groups, the activity patterns triggered by the perturbations were consistent with the activity patterns generated during the grasping and lifting of the coated object.

Dorsolateral infarction of the lower medulla: clinical-MRI study.

We describe a man with lateral medullary syndrome associated with a long-standing clumsiness of the ipsilateral upper limb. MRI showed that the clinical finding of ipsilateral clumsiness correlated with an extension of the infarction into the dorsal column nuclei but was not reflected in any involvement of the more ventral pyramidal tract. This deficit in movement control that appears superficially like a hemiparesis may result from a combination of lemniscal and spinocerebellar deficits.

[Long-term treatment with antidepressive drugs]. / Traitements antidépresseurs au long cours.

Distinction between relapse and recurrence is a major difficulty in studies assessing the efficacy of long term antidepressant treatment. A four to six months symptom-free period is required to talk of recovery from depression and plan a preventive treatment, i.e. prevention of recurrence. Compounds are not selected according to their biochemical profile; the most recent antidepressant drugs were studied in that indication through long term controlled trials. In unipolar patients, recent studies favour the prescription of high doses of antidepressant drugs during at least five years. In bipolar patients, combination of long term antidepressant to lithium treatment may be of benefit to patients whose index episode was of depressive type, but appears useless in other cases. In all cases, joint psychotherapy and the quality of the relationship between the patient and the prescribing physician influence compliance and outcome. Dysthymia, panic disorder and obsessive-compulsive disorder constitute other acknowledged cases for long term prescription of antidepressants. These indications remain empirical till controlled trials have not specifically assessed each antidepressant compound.

[New antipsychotic agents]. / Les nouveaux antipsychotiques.

In the eighties, the notions of refractory schizophrenia and of atypical neuroleptics have been described. An "atypical" neuroleptic is an effective antipsychotic drug without inducing concomitant extrapyramidal side effects. The concept of atypicity has become a new vista for research of new antipsychotic drugs. The notions of partial dopaminergic agonism, antagonism of D4 receptor, selective 5HT2 antagonism must be viewed as a source of future research and therapeutic improvement.

[Sequence in prescribing neuroleptics: a therapeutic alternative in refractory schizophrenia?]. / Séquence de prescription de neuroleptiques: une alternative thérapeutique dans les schizophrénies résistantes?

Although clozapine (CLZ) is effective in resistant schizophrenia, it fails in some cases leading to a therapeutic problem. Authors report a case of schizophrenia which resists several neuroleptic trials (including haloperidol, chlorpromazine and thioproperazine) and responds to a sequence of CLZ and amisulpride. These two atypical neuroleptics have the same main target (mesolimbic system) but have different and complementary affinities to neuromediator receptors: CLZ has strong serotoninergic and anticholinergic action, noradrenergic alpha 1 affinity and moderately active dopaminergic antagonism; amisulpride has a high and specific dopaminergic D2 antagonism when used at high posology. This clinical improvement can be related to "second treatment effect", described by Goldman in 1966: his study included two groups of refractory schizophrenic patients who received successively during two 6 months periods, 2 neuroleptics (fluphenazine and trifluperazine). Without initial therapeutic response, he noted a significant improvement only after change of neuroleptic medication. Tricyclic antidepressants may turn to be effective, after an initial failure, when they are given after an uneffective ECT trial. The same model may be applied and the clozapine-amisulpride sequence is proposed as an alternative treatment in resistant schizophrenia: even if CLZ is uneffective, it may produce carryover effects which ease the action of amisulpride. The hypothesis of an action on 5HT2-D2 antagonism is advanced. It leads to the general question of the opportunity of neuroleptic sequential prescription in resistant schizophrenia as a therapeutic option.

Maintenance ECT in intractable manic-depressive disorders.

Twenty-two patients suffering from intractable recurrent unipolar or bipolar mood disorders were enrolled in a maintenance-ECT protocol (ECT-M) for more than 18 months, with a treatment at approximately monthly intervals. Eleven have continued treatment for > 2 years. Whereas 44% of the year had been spent in the hospital with at least three episodes a year prior to ECT-M, only 7% of the year was spent in the hospital during ECT-M with only one relapse every 16 months requiring admission (p < 0.001). Forty-five percent of the patients were in full remission and 27% in partial remission according to DSM-III-R criteria. ECT-M responsiveness of rapid-cyclers and delusional depressed patients usually drug refractory has been very encouraging with full or partial remission for 100% of rapid-cyclers and 80% of delusional depressed patients.

[Hyperparathyroidism with lithium]. / Hyperparathyroïdie sous lithium.

Lithium has proved to be a highly effective preventive measure in mood disorders and an increasing number of patients are receiving long-term lithium carbonate therapy. Among other biologically and clinically important effects of lithium, the possible induction of hyperparathyroidism was first suggested in 1973 by Garfinkel et al. About thirty other case reports have since been described, but they could simply have represented the coincidental occurrence of primary hyperparathyroidism and lithium carbonate treatment in the same patients. Eleven cross-sectional studies of calcium metabolism in patients treated with lithium carbonate have been reported. Evidence of a causal relationship of lithium to hyperparathyroidism can lead to a loss of effectiveness of lithium in controlling the affective symptoms. Interestingly, coexistence with hypothyroidism is not uncommon. Low serum phosphate, high serum chloride are also observed. Bone mineral content may decrease. In addition, several studies have shown that lithium treatment increases serum magnesium level. Unusual metabolic features are associated with hyperparathyroidism and long-term lithium treatment: low urinary calcium excretion, absence of nephrolithiasis, and normal urinary cyclic AMP excretion. Lithium inhibition of PTH sensitive adenylcyclase in the kidney would explain these features. In vitro studies suggested that lithium is a potent inhibitor of several hormone responsive adenylcyclase systems. It is possible that the tissue susceptibility to adenylcyclase inhibition in an individual may decide the nature of endocrine dysfunction seen during lithium treatment. Information about the time course with which abnormalities may develop is derived from longitudinal studies. Several months to several years are needed for lithium inducing primary hyperparathyroidism. In vitro studies provide strong evidence that lithium can induce a shift in the set-point for inhibition of PTH secretion by calcium and a direct stimulation of PTH secretion. The extent to which we can extrapolate these data to the clinical situation is discussed. In vivo data from Shen an Seely are compatible with these two mechanisms. These alterations should cause parathyroid hyperplasia. The possibility that a generalized parathyroid stimulus might lead to formation of a single adenima is not proved. Several recommendations regarding parathyroid function in patients receiving lithium have been suggested. Measurement of total calcium and serum proteins or of serum calcium ion values when available should be performed before therapy is begun. If elevated values are obtained, lithium treatment should be deferred and evaluation for hyperparathyroidism performed. Serum calcium should be monitored periodically during lithium treatment. Sustained hypercalcemia or true hyperparathyroidism require parathyroidectomy. If hypercalcemia is mild without complication and psychiatric symptoms well controlled, perhaps surgery should not be employed.

Covert processing of information in hemianesthesia: a case report.

A 69-year-old patient with a cortical lesion of the primary sensory area showed a surprising sensorimotor control of the anesthetized arm. This observation suggested the existence of residual capacities of somesthetic information processing. This hypothesis was tested using a forced choice procedure on four tasks involving discrimination between different characteristics of the tactual-kinaesthetic stimulus. Whereas the patient was unable to identify the direction of movement or to discriminate between different letters, she could detect the occurrence of the stimulation or its dynamic quality significantly well. These results are discussed in reference to an anatomo-functional organization analogous to the one underlying the processing of visual information.

[Lithium in the treatment of refractory depression]. / Le lithium dans le traitement des dépressions résistantes.

The definition of treatment-resistant depression is variously interpreted. There is no agreement of different authors on its meaning. The present vagueness of criteria for the diagnosis of a refractory depression contrasts with the many studies reporting potentiation of antidepressants by lithium. De Montigny in 1981, after early works by Zall and by Lingjaerde, initiated this approach that still remains poorly understood in terms of biochemical mechanisms. A review of the controlled studies shows that the delay of antidepressant action varies and the term "lithium potentiation" does not seem totally relevant. From a pharmacological point of view, several types of data suggest a synergic potentiation rather than a true potentiation. This effect applies to all classes of antidepressants and improves about 50% of patients who did not respond positively to an adequate treatment received during 4 to 6 weeks. Many questions remain unanswered particularly concerning the lithium levels, factors predicting a positive response and the strategy for the maintenance treatment. Studies are necessary in order to compare the relevance of this potentiation technique with the mere substitution by another antidepressant and to understand the biochemical mechanisms underlying the synergic effect.