HF-rTMS treatment decreases psychomotor retardation in medication-resistant melancholic depression

Repetitive Transcranial Magnetic Stimulation (rTMS) applied to the left dorsolateral prefrontal cortex (DLPFC) might be a promising treatment strategy for depression. As one of the key features of melancholic depression is disturbances in psychomotor activity, we wanted to evaluate whether HF-rTMS treatment could influence psychomotor symptoms. Twenty antidepressant-free unipolar melancholic depressed patients, all at least stage III medication-resistant, were studied. All were treated with 10 sessions of High-Frequency (HF)-rTMS applied to the left dorsolateral prefrontal cortex (DLPFC) under MRI guidance. Forty percent of the patients showed a reduction of at least 50% on their initial 17-item Hamilton Depression Rating Score (HDRS) scale and were defined as clinical responders. Regardless of clinical outcome HF-rTMS treatment resulted in significant decreases on the Depressive Retardation Rating Scale (DRRS) scores. Although this was an open study in a relatively small sample, our results suggest that HF-rTMS might act on the ‘psychomotor’ level and these findings could add some further information as to why this kind of treatment can be beneficial for severely depressed patients of the melancholic subtype.     

Relationships between psychomotor retardation and EEG power spectrum in major depression.

In 63 depressed patients, the associations between severity of depression, psychomotor retardation, assessed by the Bech-Rafaelsen Melancholia Scale, and EEG spectral analysis were examined. Slow EEG activity (theta 2/alpha 1 bands) was positively and fast activity (alpha 3/beta bands) negatively correlated with the observed retardation. Out of the four retardation subitems (motor, verbal, intellectual and emotional), motor retardation was closest correlated with slow EEG activity.     

Frontal white matter integrity is related to psychomotor retardation in major depression

Altered frontal white matter integrity has been reported in major depression. Still, the behavioral correlates of these alterations are not established. In healthy subjects, motor activity correlated with white matter integrity in the motor system. To explore the relation of white matter integrity and motor activity in major depressive disorder, we investigated 21 medicated patients with major depressive disorder and 21 matched controls using diffusion tensor imaging and wrist actigraphy at the same day. Patients had lower activity levels (AL) compared with controls. Fractional anisotropy (FA) differed between groups in frontal white matter regions and the posterior cingulum. AL was linearly associated with white matter integrity in two clusters within the motor system. Controls had an exclusive positive association of FA and AL in white matter underneath the right dorsal premotor cortex. Only patients had a positive association within the posterior cingulum. Furthermore, patients had negative associations of FA and AL underneath the left primary motor cortex and within the left parahippocampal gyrus white matter. These differences in the associations between structure and behavior may contribute to well-known impaired motor planning or gait disturbances in major depressive disorder. Therefore, signs of psychomotor slowing in major depressive disorder may be linked to changes of the white matter integrity of the motor system.     

Slow brain potentials after withdrawal of control

Summary The present experiment was designed to replicate and extend the previous finding of an increased postimperative negative slow brain potential shift (PINV) in healthy subjects following an unexpected change from the condition of control over an aversive imperative stimulus to that of loss of control. Two groups of 16 male students each participated in a constant-foreperiod reaction time paradigm with two warning stimuli (WS), each of 6 s duration, followed by two imperative stimuli (IS) of either aversive (loud noise) or neutral (soft tone) quality. The experimental subjects could terminate each IS by pressing a microswitch within 300 ms of IS-onset. After they had experienced this contingency for 40 trials, control was withdrawn in that the IS lasted for 5 s during another 40-trial block, irrespective of the actual motor response of the subject. The yoked control subjects received the same stimuli and performed the same motor response as the experimental subjects, but experienced no contingency between response and IS-termination. EEGs were recorded monopolarly from Fz, Cz, and Pz. In response to the unexpectedly uncontrollable aversive IS, the experimental subjects showed a pronounced PINV over frontal areas, while no comparable PINV developed in yoked controls. Experimental subjects showed no PINV during the first trial block (control conditions), and in response to the neutral uncontrollable IS. Statistical analyses of principle components documented that the PINV can be considered an independent endogenous component.Research was supported by the Deutsche Forschungsgemeinschaft grant Bi 195.     

Slow brain potentials and the "tunnel effect"

The present study investigated electrocortical concomitants of the "tunnel effect." The tunnel effect refers to the following perceptual phenomenon: if a continuously moving object disappears behind a shield ("enters a tunnel") the observer has the impression that the same object continues to move with the time point of reappearance usually being underestimated. In the present study, an object moved across a tv-screen for 6 s; it either disappeared behind a shield (tunnel condition), disappeared at once (explosion condition), or remained visible until the end of its trajectory (control condition). Subjects had to press a button whenever they believed that the object had arrived at its trajectory's end. The object's flight was accompanied by a continuously rising slow negative shift of the EEG that resembled the contingent negative variation (CNV). Either type of object disappearance produced a positive-going potential that may reflect brain processes associated with memory rehearsal and/or time estimation. A late P300-like positivity was prominent under tunnel conditions only. Response latency was shorter under disappearance than under control conditions. The positive deflection is discussed as sign of amodal brain processing (memory rehearsal and/or time estimation). The P300-like wave elicited by the object's disappearance activates these memory representations. Based on these considerations, an attempt was made to interpret the premature motor responses, which are commonly observed for tunnel conditions but not for other time estimation tasks.     

Slow wave field potentials in the rat brain during the estrous cycle

Twenty-one rats were implanted with chronic electrodes in the amygdala, preoptic area, and arcuate nucleus-median eminence region in an effort to learn more about electrical activity in the limbic system and the relationship to the estrous cycle. Slow wave field potentials from these three areas were recorded for ten minutes of each half-hour between 10:00 a.m. and 3:30 p.m. each day of the four-day estrous cycle. These recordings were analyzed for amount of correlation and direction of conduction between pairs of electrodes and for conduction times between pairs of sites. Slow wave field potential conduction from the amygdala to the preoptic area during the “critical period” on the day of proestrus lasts longer and takes longer en route than at other times of the cycle. This is statistically significant at p<0.0002 and implies a change in the conducting pathway during this time.     

Action monitoring in major depressive disorder with psychomotor retardation

Major depressive disorder (MDD) is characterized by disturbances of mood and affect, but also by a distinct pattern of psychomotor and cognitive deficits such as motor retardation and impaired executive functioning. An important aspect of executive functioning is performance monitoring, i.e., a continuous checking whether intended action goals have been reached and whether correction of the applied strategy is necessary. A well-known marker for action monitoring is the error negativity (Ne) or error-related negativity (ERN), an event-related potential (ERP) component generated in the anterior cingulate cortex (ACC) following erroneous responses. To date, Ne/ERN amplitudes have been investigated in moderately depressed patients only. The present study is the first to investigate action monitoring in severely depressed patients (mean Hamilton score=28.4). In addition, the patients' psychomotor performance was assessed to see whether there is a relationship between action monitoring and psychomotor retardation. Behavioural and ERP measurements were obtained during performance on a speeded two-choice reaction task in 26 patients with MDD and 25 healthy, matched controls. Psychomotor performance measures were speed of simple movements in various psychomotor tasks and the score on the Salpêtrière retardation rating scale (SRRS). Relative to the controls, the patients' behavioural results revealed a similar, but slower performance pattern. Overall between-group differences were demonstrated for the error positivity (Pe) amplitudes, but not for the Ne/ERN amplitudes. However, correlations of the Ne/ERN amplitude with several psychomotor variables were strong. In the depressed patients taking benzodiazepines an additional attenuation of Ne/ERN amplitudes was observed. Only severely depressed patients manifesting retardation showed impeded action monitoring. The correlations between action monitoring and psychomotor performance indicate that in MDD these two processes are highly interdependent, both being deregulated. Moreover, the same network of brain regions is likely to be implicated in both processes.     

Late-infantile form galactosialidosis with psychomotor retardation and spastic paraparesis

We described a case of late-infantile form of galactosialidosis. This male patient was a product of normal pregnancy. His parents were first cousins. He first sat at eight months, walked and talked at two years of age. His gait gradually became unsteady and he was diagnosed as spastic paraparesis at the age of five years. Abnormally slow learning was first pointed out at seven years of age. At the age of nine years, we evaluated him in detail at our university hospital. Physical examination revealed a short stature for his age, slightly coarse face, short neck, funnel chest, genu, pes and hallucis valgus. Corneal clouding, hernia and angiokeratoma were not found. Neurological examination showed mental retardation, bilateral optic atrophy without cherry-red spots, and spastic and slightly ataxic gait. Slight muscular atrophy with weakness was also seen in the extremities, more remarkable in the lower limbs. Deep tendon reflexes were hyperactive with bilateral ankle clonus and no extensor planter response. Routine examination of blood, urine and cerebrospinal fluid were normal except for approximately 10% lymphocytes containing cytoplasmic vacuoles. X-ray films of the backbone exhibited vertebral plana with anterior breaking at the second lumbar vertebra level. The electroencephalography showed the multiple spike and slow wave complexes. Brain CT depicted the atrophy of cerebellum. The activities of sialidase and beta-galactosidase were markedly reduced in white blood cells and cultured skin fibroblasts in this patient. His urinary excretion of sialyloligosaccharides increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Psychomotor retardation and anhedonia in depression

Anhedonia, the inability to experience pleasure, and observed changes in psychomotor performance are frequent psychopathological phenomena in major depression with possible common neurobiological mechanisms. Interest, pleasure and reactivity to pleasurable stimuli contribute to movement generation and observable behaviour. Therefore the relationship between anhedonia and psychomotor retardation was studied in 48 depressed patients. Subjectively experienced anhedonia correlated with self-rated but not with observer-rated global severity of depression. There was a significant correlation between anhedonia and psychomotor retardation assessed with the Widlöcher Retardation Scale. The results suggest the existence of an empirical relationship between reduced ability to experience pleasure and observable psychomotor retardation in depression. Specific measures of psychomotor phenomena may provide further insights into the relationship between observable behaviour and self-experienced symptoms in depression.     

Autosomal recessive microcephaly with severe psychomotor retardation.

Autosomal recessive microcephaly has long been recognized in association with normal early motor development and mild to severe mental retardation. We report three sibling pairs with microcephaly and severe neurological impairment. These cases and other sibling pairs reported in the literature illustrate that microcephaly with spasticity and severe mental retardation may also have autosomal recessive inheritance. Furthermore this severely affected group of patients forms a significant proportion of cases of genetic microcephaly. We looked for specific morphological features to identify these forms of genetic microcephaly for genetic counselling, but failed to find characteristic abnormalities among our group of patients.     

Congenital alopecia, seizures, and psychomotor retardation in three siblings

Three siblings, devoid of hair at birth, had an unusual autosomal recessive disorder characterized by universal congenital alopecia, microcephaly, seizures, psychomotor retardation, and severe growth failure. Metabolic and chromosome studies were normal. Skin biopsies disclosed immature hair follicles, some of which were filled with keratotic material but had no hair shafts. Neuropathologic features included cerebral cortical hypoplasia, neuronal depletion, and microcalcifications. The familial occurrence of universal congenital alopecia conjoined with nonprogressive central nervous system abnormalities in this and other kindreds defines a nosologic group of neurocutaneous disorders in which congenital alopecia is the solitary cutaneous manifestation.     

Carnitine palmitoyltransferase deficiency in a patient with severe psychomotor retardation

A 13-year-old girl who had severe brain damage due to unknown prenatal cause presented rhabdomyolysis triggered by a mild viral infection. Her muscle biopsy revealed mild variation in fiber size and type 2 fiber atrophy without excess lipid storage. Biochemical analysis of the biopsied material showed decreased carnitine palmitoyltransferase (CPT) activity (15% of the control). Serum and urinary carnitine levels were normal. Skeletal muscle CT scanning showed multiple low density spots. The patient was diagnosed as having CPT deficiency. She recovered from rhabdomyolysis without renal failure after a month with conservative therapy. CPT deficiency is usually found in young healthy persons. This is the first case report of CPT deficiency which presented severe psychomotor retardation since neonatal period.     

Electrophysiological and behavioral correlates of psychomotor responsivity in depression

Psychomotor retardation is a frequently observed clinical feature of depressive states. This study attempted to assess the relationship between response slowness and central nervous system (CNS) activity by examining cortical evoked potentials (EPs) during psychomotor task performance. Patients consisted of 21 women who met Research Diagnostic Criteria (RDC) and exhibited a minimum Hamilton Rating Scale for Depression score of 18 at the end of a drug washout period, the scheduled time of testing. The same number of normal women with no history of psychiatric illness were employed as controls. Cortical EPs from Cz and integrated electromyogram (EMG) from the dominant forearm extensor were recorded and time-locked to warning and imperative stimuli of a standard, two-choice, fixed foreperiod reaction time (RT) task, which yielded behavioral measures of decision time (DT) and movement time (MT). Analysis focused on behavioral RTs, latency and amplitudes of EMG, sensory and slow cortical (CNV) EPs, and measures of input time (IPT), central processing time (CPT), and motor execution time (MET), derived from combinations of EP and EMG peak latencies. Patients exhibited slower DT and MT response times, delayed EMG latencies, and attenuated EP amplitudes. The derived CPT measure was also significantly longer in patients. These findings support the view that a central dysfunction is implicated in psychomotor retardation, and the results are discussed in relation to information processing theory.