Overt Motor Research Articles

The color red attracts attention in an emotional context. An ERP study.

The color red is known to influence psychological functioning, having both negative (e.g., blood, fire, danger), and positive (e.g., sex, food) connotations. The aim of our study was to assess the attentional capture by red-colored images, and to explore the modulatory role of the emotional valence in this process, as postulated by Elliot and Maier (2012) color-in-context theory. Participants completed a dot-probe task with each cue comprising two images of equal valence and arousal, one containing a prominent red object and the other an object of different coloration. Reaction times were measured, as well as the event-related lateralizations of the EEG. Modulation of the lateralized components revealed that the color red captured and later held the attention in both positive and negative conditions, but not in a neutral condition. An overt motor response to the target stimulus was affected mainly by attention lingering over the visual field where the red cue had been flashed. However, a weak influence of the valence could still be detected in reaction times. Therefore, red seems to guide attention, specifically in emotionally-valenced circumstances, indicating that an emotional context can alter color’s impact both on attention and motor behavior.

Androgen-dependent loss of muscle BDNF mRNA in two mouse models of SBMA

Transgenic expression of neurotrophic factors in skeletal muscle has been found to protect mice from neuromuscular disease, including spinal bulbar muscular atrophy (SBMA), triggering renewed interest in neurotrophic factors as therapeutic agents for treating neuromuscular disease. Because SBMA is an androgen-dependent disease, and brain-derived neurotrophic factor (BDNF) mediates effects of androgens on neuromuscular systems, we asked whether BDNF expression is impaired in two different transgenic (Tg) mouse models of SBMA, the so called “97Q” and “myogenic” SBMA models. The 97Q model globally overexpresses a full length human AR with 97 glutamine repeats whereas the myogenic model of SBMA overexpresses a wild-type rat androgen receptor (AR) only in skeletal muscle fibers. Using quantitative PCR, we find that muscle BDNF mRNA declines in an androgen-dependent manner in both models, paralleling changes in motor function, with robust deficits (6–8 fold) in both fast and slow twitch muscles of impaired Tg males. Castration rescues or reverses disease-related deficits in muscle BDNF mRNA in both models, paralleling its effect on motor function. Moreover, when disease is acutely induced in Tg females, both motor function and muscle BDNF mRNA expression plummet, with the deficit in muscle BDNF emerging before overt motor dysfunction. That androgen-dependent motor dysfunction is tightly associated with a robust and early down-regulation of muscle BDNF mRNA suggests that BDNF delivered to skeletal muscle may have therapeutic value for SBMA.

Effect of hydroalcoholic extract of leaves of Colocasia esculenta on marble-burying behavior in mice: Implications for obsessive–compulsive disorder

Context: Over the past decades, the inhibition of spontaneous burying of glass marbles by mice has been used as an index of anxiolytic drug action in the so-called marble-burying test. Although Colocasia esculenta Linn. (Araceae), commonly known as elephant ear (English), possesses several medicinal properties, little is known for its use in neurological activity.Objective: The current research evaluated the anti-obsessive–compulsive disorder (anti-compulsive) activity of the hydroalcoholic extract of leaves of Colocasia esculenta (HECE) for the first time using the marble-burying behavior test in mice.Materials and methods: In the present study, the effect of HECE (25 and 50 mg/kg) intraperitoneally (i.p.) was examined using the marble-burying behavior test, which is an animal model of obsessive compulsive disorder (OCD), using Swiss albino mice.Results and discussion: The acute toxicity studies showed that the LD50 value of the HECE in mice was 1000 mg/kg by i.p. route. The effect of HECE (25 and 50 mg/kg, i.p.) was characterized by significant reduction in the number of buried marbles as compared with the control group (p < 0.001). The effect of HECE was comparable with that of fluoxetine (5 mg/kg, i.p.) – a reference standard drug used in the treatment of obsessive–compulsive disorder (p < 0.001). Fluoxetine and HECE do not produce any overt motor dysfunction.Conclusions: The results of the study for the first time show that the plant possesses anti-compulsive activity, confirming the traditional claims. Future research should focus on the identification and the anti-compulsive activity of the constituents from this plant.

Ignition's glow: Ultra-fast spread of global cortical activity accompanying local "ignitions" in visual cortex during conscious visual perception.

Despite extensive research, the spatiotemporal span of neuronal activations associated with the emergence of a conscious percept is still debated. The debate can be formulated in the context of local vs. global models, emphasizing local activity in visual cortex vs. a global fronto-parietal "workspace" as the key mechanisms of conscious visual perception. These alternative models lead to differential predictions with regard to the precise magnitude, timing and anatomical spread of neuronal activity during conscious perception. Here we aimed to test a specific aspect of these predictions in which local and global models appear to differ - namely the extent to which fronto-parietal regions modulate their activity during task performance under similar perceptual states. So far the main experimental results relevant to this debate have been obtained from non-invasive methods and led to conflicting interpretations. Here we examined these alternative predictions through large-scale intracranial measurements (Electrocorticogram - ECoG) in 43 patients and 4445 recording sites. Both ERP and broadband high frequency (50-150 Hz - BHF) responses were examined through the entire cortex during a simple 1-back visual recognition memory task. Our results reveal short latency intense visual responses, localized first in early visual cortex followed (at ∼200 ms) by higher order visual areas, but failed to show significant delayed (300 ms) visual activations. By contrast, oddball image repeat events, linked to overt motor responses, were associated with a significant increase in a delayed (300 ms) peak of BHF power in fronto-parietal cortex. Comparing BHF responses with ERP revealed an additional peak in the ERP response - having a similar latency to the well-studied P3 scalp EEG response. Posterior and temporal regions demonstrated robust visual category selectivity. An unexpected observation was that high-order visual cortex responses were essentially concurrent (at ∼200 ms) with an ultra-fast spread of signals of lower magnitude that invaded selected sites throughout fronto-parietal cortical areas. Our results are compatible with local models in demonstrating a clear task-dependence of the 300 ms fronto-parietal activation. However, they also reveal a more global component of low-magnitude and poor content selectivity that rapidly spreads into fronto-parietal sites. The precise functional role of this global "glow" remains to be elucidated.

19. Hippocampal negative event-related potential recorded in humans is not time-locked to the motor response execution

A hippocampal-prominent event-related potential (ERP) with a peak latency at around 450 ms is consistently observed as a correlate of hippocampal activity during various cognitive tasks. Some intracranial EEG studies demonstrated that the amplitude of this hippocampal potential was greater in response to stimuli requiring an overt motor response, in comparison with stimuli for which no motor response is required. These findings could indicate that hippocampal evoked activity is related to movement execution as well as stimulus evaluation and associated memory processes. The aim of the present study was to investigate the temporal relationship between the hippocampal negative potential latency (hippocampal slow negativity, hipp SNe) and motor responses. We analyzed ERPs recorded with 22 depth electrodes implanted into the hippocampi of 11 epileptic patients. Subjects were instructed to press a button after the presentation of a tone. All investigated hippocampi generated a prominent negative event-related potential peaking at approximately 420 ms. In 16 from 22 cases we found that the ERP latency did not correlate with the reaction time; in different subjects, this potential could either precede or follow the motor response. Our results indicate that hippocampal slow negativity is not time-locked to the motor response. We suggest that hippocampal evoked activity, recorded in a simple sensorimotor task, is related to the full-value evaluation of stimulus significance within the context of situation.

Adaptive coding of orofacial and speech actions in motor and somatosensory spaces with and without overt motor behavior.

Studies of speech motor control suggest that articulatory and phonemic goals are defined in multidimensional motor, somatosensory, and auditory spaces. To test whether motor simulation might rely on sensory-motor coding common with those for motor execution, we used a repetition suppression (RS) paradigm while measuring neural activity with sparse sampling fMRI during repeated overt and covert orofacial and speech actions. RS refers to the phenomenon that repeated stimuli or motor acts lead to decreased activity in specific neural populations and are associated with enhanced adaptive learning related to the repeated stimulus attributes. Common suppressed neural responses were observed in motor and posterior parietal regions in the achievement of both repeated overt and covert orofacial and speech actions, including the left premotor cortex and inferior frontal gyrus, the superior parietal cortex and adjacent intraprietal sulcus, and the left IC and the SMA. Interestingly, reduced activity of the auditory cortex was observed during overt but not covert speech production, a finding likely reflecting a motor rather an auditory imagery strategy by the participants. By providing evidence for adaptive changes in premotor and associative somatosensory brain areas, the observed RS suggests online state coding of both orofacial and speech actions in somatosensory and motor spaces with and without motor behavior and sensory feedback.

Functional resting-state connectivity of the human motor network: Differences between right- and left-handers

Handedness is associated with differences in activation levels in various motor tasks performed with the dominant or non-dominant hand. Here we tested whether handedness is reflected in the functional architecture of the motor system even in the absence of an overt motor task. Using resting-state functional magnetic resonance imaging we investigated 18 right- and 18 left-handers. Whole-brain functional connectivity maps of the primary motor cortex (M1), supplementary motor area (SMA), dorsolateral premotor cortex (PMd), pre-SMA, inferior frontal junction and motor putamen were compared between right- and left-handers. We further used a multivariate linear support vector machine (SVM) classifier to reveal the specificity of brain regions for classifying handedness based on individual resting-state maps. Using left M1 as seed region, functional connectivity analysis revealed stronger interhemispheric functional connectivity between left M1 and right PMd in right-handers as compared to left-handers. This connectivity cluster contributed to the individual classification of right- and left-handers with 86.2% accuracy. Consistently, also seeding from right PMd yielded a similar handedness-dependent effect in left M1, albeit with lower classification accuracy (78.1%). Control analyses of the other resting-state networks including the speech and the visual network revealed no significant differences in functional connectivity related to handedness. In conclusion, our data revealed an intrinsically higher functional connectivity in right-handers. These results may help to explain that hand preference is more lateralized in right-handers than in left-handers. Furthermore, enhanced functional connectivity between left M1 and right PMd may serve as an individual marker of handedness.

Functional MRI evidence for fine motor praxis dysfunction in children with persistent speech disorders

AbstractChildren with persistent speech disorders (PSD) often present with overt or subtle motor deficits; the possibility that speech disorders and motor deficits could arise from a shared neurological base is currently unknown. Functional MRI (fMRI) was used to examine the brain networks supporting fine motor praxis in children with PSD and without clinically identified fine motor deficits. MethodsThis case-control study included 12 children with PSD (mean age 7.42 years, four female) and 12 controls (mean age 7.44 years, four female). Children completed behavioral evaluations using standardized motor assessments and parent reported functional measures. During fMRI scanning, participants completed a cued finger tapping task contrasted passive listening. A general linear model approach identified brain regions associated with finger tapping in each group and regions that differed between groups. The relationship between regional fMRI activation and fine motor skill was assessed using a regression analysis. ResultsChildren with PSD had significantly poorer results for rapid speech production and fine motor praxis skills, but did not differ on classroom functional skills. Functional MRI results showed that children with PSD had significantly more activation in the cerebellum during finger tapping. Positive correlations between performance on a fine motor praxis test and activation multiple cortical regions were noted for children with PSD but not for controls. ConclusionsOver-activation in the cerebellum during a motor task may reflect a subtle abnormality in the non-speech motor neural circuitry in children with PSD.

Cerebellar-motor dysfunction in schizophrenia and psychosis-risk: the importance of regional cerebellar analysis approaches.

Motor abnormalities in individuals with schizophrenia and those at-risk for psychosis are well documented. An accumulating body of work has also highlighted motor abnormalities related to cerebellar dysfunction in schizophrenia including eye-blink conditioning, timing, postural control, and motor learning. We have also recently found evidence for motor dysfunction in individuals at ultra high-risk for psychosis (1–3). This is particularly relevant as the cerebellum is thought to be central to the cognitive dysmetria model of schizophrenia, and these overt motor signs may point to more general cerebellar dysfunction in the etiology of psychotic disorders. While studies have provided evidence indicative of motor cerebellar dysfunction in at-risk populations and in schizophrenia, findings with respect to the cerebellum have been mixed. One factor potentially contributing to these mixed results is the whole-structure approach taken when investigating the cerebellum. In non-human primates, there are distinct closed-loop circuits between the cerebellum, thalamus, and brain with motor and non-motor cortical regions. Recent human neuroimaging has supported this finding and indicates that there is a cerebellar functional topography (4), and this information is being missed with whole-structure approaches. Here, we review cerebellar-motor dysfunction in individuals with schizophrenia and those at-risk for psychosis. We also discuss cerebellar abnormalities in psychosis, and the cerebellar functional topography. Because of the segregated functional regions of the cerebellum, we propose that it is important to look at the structure regionally in order to better understand its role in motor dysfunction in these populations. This is analogous to approaches taken with the basal ganglia, where each region is considered separately. Such an approach is necessary to better understand cerebellar pathophysiology on a macro-structural level with respect to the pathogenesis of psychosis.

Differential loss of thalamostriatal and corticostriatal input to striatal projection neuron types prior to overt motor symptoms in the Q140 knock-in mouse model of Huntington's disease.

Motor slowing and forebrain white matter loss have been reported in premanifest Huntington's disease (HD) prior to substantial striatal neuron loss. These findings raise the possibility that early motor defects in HD may be related to loss of excitatory input to striatum. In a prior study, we showed that in the heterozygous Q140 knock-in mouse model of HD that loss of thalamostriatal axospinous terminals is evident by 4 months, and loss of corticostriatal axospinous terminals is evident at 12 months, before striatal projection neuron pathology. In the present study, we specifically characterized the loss of thalamostriatal and corticostriatal terminals on direct (dSPN) and indirect (iSPN) pathway striatal projection neurons, using immunolabeling to identify thalamostriatal (VGLUT2+) and corticostriatal (VGLUT1+) axospinous terminals, and D1 receptor immunolabeling to distinguish dSPN (D1+) and iSPN (D1−) synaptic targets. We found that the loss of corticostriatal terminals at 12 months of age was preferential for D1+ spines, and especially involved smaller terminals, presumptively of the intratelencephalically projecting (IT) type. By contrast, indirect pathway D1− spines showed little loss of axospinous terminals at the same age. Thalamostriatal terminal loss was comparable for D1+ and D1− spines at both 4 and 12 months. Regression analysis showed that the loss of VGLUT1+ terminals on D1+ spines was correlated with a slight decline in open field motor parameters at 12 months. Our overall results raise the possibility that differential thalamic and cortical input loss to SPNs is an early event in human HD, with cortical loss to dSPNs in particular contributing to premanifest motor slowing.

Onset of Huntington's disease: can it be purely cognitive?

Knowledge of the cognitive manifestation of Huntington's disease has burgeoned over the past two decades. Many studies from independent datasets have shown that cognitive impairment is evident before motor diagnosis, and annual cognitive decline is a robust marker of disease progression. Additionally, cognition is a critical concern to patients and families and is associated with meaningful outcomes, including functional capacity, driving, loss of accustomed work, and quality of life. In the past few years, Huntington's disease animal models of cognition have increased, preparing for preclinical experimental therapeutics with cognitive endpoints. A longitudinal analysis of cognitive variables was conducted with 559 gene-positive cases and 233 controls showing no signs of motor abnormalities over approximately a 3-year period. Results show statistically significant differences in rate of annual change for some cognitive variables, such that the cases group had worsening performance over time. These findings show that cognitive deterioration can be seen in persons with the Huntington's disease gene expansion with no overt motor signs or symptoms, suggesting that cognitive onset of Huntington's disease may precede motor.

The first knockin mouse model of episodic ataxia type 2

Episodic ataxia type 2 (EA2) is an autosomal dominant disorder associated with attacks of ataxia that are typically precipitated by stress, ethanol, caffeine or exercise. EA2 is caused by loss-of-function mutations in the CACNA1A gene, which encodes the α1A subunit of the CaV2.1 voltage-gated Ca2+ channel. To better understand the pathomechanisms of this disorder in vivo, we created the first genetic animal model of EA2 by engineering a mouse line carrying the EA2-causing c.4486T>G (p.F1406C) missense mutation in the orthologous mouse Cacna1a gene. Mice homozygous for the mutated allele exhibit a ~70% reduction in CaV2.1 current density in Purkinje cells, though surprisingly do not exhibit an overt motor phenotype. Mice hemizygous for the knockin allele (EA2/− mice) did exhibit motor dysfunction measurable by rotarod and pole test. Studies using Cre-flox conditional genetics explored the role of cerebellar Purkinje cells or cerebellar granule cells in the poor motor performance of EA2/− mice and demonstrate that manipulation of either cell type alone did not cause poor motor performance. Thus, it is possible that subtle dysfunction arising from multiple cell types is necessary for the expression of certain ataxia syndromes.

Coherence and Consciousness: Study of Fronto-Parietal Gamma Synchrony in Patients with Disorders of Consciousness.

Evaluation of consciousness needs to be supported by the evidence of brain activation during external stimulation in patients with unresponsive wakefulness syndrome (UWS). Assessment of patients should include techniques that do not depend on overt motor responses and allow an objective investigation of the spontaneous patterns of brain activity. In particular, electroencephalography (EEG) coherence allows to easily measure functional relationships between pairs of neocortical regions and seems to be closely correlated with cognitive or behavioral measures. Here, we show the contribution of higher order associative cortices of patients with disorder of consciousness (N=26) in response to simple sensory stimuli, such as visual, auditory and noxious stimulation. In all stimulus modalities an increase of short-range parietal and long-range fronto-parietal coherences in gamma frequencies were seen in the controls and minimally conscious patients. By contrast, UWS patients showed no significant modifications in the EEG patterns after stimulation. Our results suggest that UWS patients can not activate associative cortical networks, suggesting a lack of information integration. In fact, fronto-parietal circuits result to be connectively disrupted, conversely to patients that exhibit some form of consciousness. In the light of this, EEG coherence can be considered a powerful tool to quantify the involvement of cognitive processing giving information about the integrity of fronto-parietal network. This measure can represent a new neurophysiological marker of unconsciousness and help in determining an accurate diagnosis and rehabilitative intervention in each patient.

Focal dystonia and the Sensory-Motor Integrative Loop for Enacting (SMILE).

Performing accurate movements requires preparation, execution, and monitoring mechanisms. The first two are coded by the motor system, the latter by the sensory system. To provide an adaptive neural basis to overt behaviors, motor and sensory information has to be properly integrated in a reciprocal feedback loop. Abnormalities in this sensory-motor loop are involved in movement disorders such as focal dystonia, a hyperkinetic alteration affecting only a specific body part and characterized by sensory and motor deficits in the absence of basic motor impairments. Despite the fundamental impact of sensory-motor integration mechanisms on daily life, the general principles of healthy and pathological anatomic–functional organization of sensory-motor integration remain to be clarified. Based on the available data from experimental psychology, neurophysiology, and neuroimaging, we propose a bio-computational model of sensory-motor integration: the Sensory-Motor Integrative Loop for Enacting (SMILE). Aiming at direct therapeutic implementations and with the final target of implementing novel intervention protocols for motor rehabilitation, our main goal is to provide the information necessary for further validating the SMILE model. By translating neuroscientific hypotheses into empirical investigations and clinically relevant questions, the prediction based on the SMILE model can be further extended to other pathological conditions characterized by impaired sensory-motor integration.

Cortical representations of confidence in a visual perceptual decision.

To date the exact neuronal implementation of decision confidence has been subject to little research. Here we explore electroencephalographic correlates of human choice certainty in a visual motion discrimination task for either spatial attention or motor effector cue instructions. We demonstrate electrophysiological correlates of choice certainty that evolve as early as 300 ms after stimulus onset and resemble the primary visual motion representations in early visual cortex. These correlates do not emerge unless or until the subject unambiguously knows which of the competing visual stimuli is actually relevant to behaviour. They extend beyond stimulus presentation up to the motor response but are independent of the motor effector. Our findings suggest that perceptual confidence evolves in parallel with representations of stimulus properties and is dedicated to one specific aspect of the visual world. Its electroencephalographic correlates can be disentangled from representations of sensory evidence, objective discrimination performance and overt motor behaviour.

Tool use imagery triggers tool incorporation in the body schema.

Tool-use has been shown to modify the way the brain represents the metrical characteristics of the effector controlling the tool. For example, the use of tools that elongate the physical length of the arm induces kinematic changes affecting selectively the transport component of subsequent free-hand movements. Although mental simulation of an action is known to involve -to a large extent- the same processes as those at play in overt motor execution, whether tool-use imagery can yield similar effects on the body representation remains unknown. Mentally simulated actions indeed elicit autonomic physiological responses and follow motor execution rules that are comparable to those associated with the correspondent overt performance. Therefore, here we investigated the effects of the mental simulation of actions performed with a tool on the body representation by studying subsequent free-hand movements. Subjects executed reach to grasp movements with their hand before and after an imagery task performed with either a tool elongating their arm length or, as a control, with their hand alone. Two main results were found: First, in agreement with previous studies, durations of imagined movements performed with the tool and the hand were similarly affected by task difficulty. Second, kinematics of free-hand movements was affected after tool-use imagery, but not hand-use imagery, in a way similar to that previously documented after actual tool-use. These findings constitute the first evidence that tool-use imagery is sufficient to affect the representation of the user's arm.

Balancing cognitive control: How observed movements influence motor performance in a task with balance constraints

We investigated the influence of observed movements on executed movements in a task requiring lifting one foot from the floor while maintaining whole-body balance. Sixteen young participants (20–30years) performed foot lift movements, which were either cued symbolically by a letter (L/R, indicating to lift the left/right foot) or by a short movie showing a foot lift movement. In the symbol cue condition, stimuli from the movie cue condition were used as distractors, and vice versa. Anticipatory postural adjustments (APAs) and actual foot lifts were recorded using force plates and optical motion capture. Foot lift responses were generally faster in response to the movie compared to the symbol cue condition. Moreover, incongruent movement distractors interfered with performance in the symbol cue condition, as shown by longer response times and increased number of APAs. Latencies of the first (potentially wrong) APA in a trial were shorter for movie compared to symbol cues but were not affected by cue-distractor congruency. Amplitude of the first APA was smaller when it was followed by additional APAs compared to trials with a single APA. Our results show that automatic imitation tendencies are integrated with postural control in a task with balance constraints. Analysis of the number, timing and amplitude of APAs indicates that conflicts between intended and observed movements are not resolved at a purely cognitive level but directly influence overt motor performance, emphasizing the intimate link between perception, cognition and action.

Poster #S23 UPREGULATION OF STRIATAL DOPAMINE D2 RECEPTORS RESULTS IN PERSISTENT ALTERATIONS IN PRE-SYNAPTIC DOPAMINE FUNCTION

Huntington's disease (HD) is an inherited neurodegenerative disorder that is classically defined by a triad of movement and cognitive and psychiatric abnormalities with a well-established pathology that affects the dopaminergic systems of the brain. This has classically been described in terms of an early loss of dopamine D2 receptors (D2R), although interestingly the treatments most effectively used to treat patients with HD block these same receptors. We therefore sought to examine the dopaminergic system in HD not only in terms of striatal function but also at extrastriatal sites especially the hippocampus, given that transgenic (Tg) mice also exhibit deficits in hippocampal-dependent cognitive tests and a reduction in adult hippocampal neurogenesis. We showed that there was an early reduction of D2R in both the striatum and dentate gyrus (DG) of the hippocampus in the R6/1 transgenic HD mouse ahead of any overt motor signs and before striatal neuronal loss. Despite downregulation of D2Rs in these sites, further reduction of the dopaminergic input to these sites by either medial forebrain bundle lesions or receptor blockade using sulpiride was able to improve both deficits in motor performance and adult hippocampal neurogenesis. In contrast, a reduction in dopaminergic innervation of the neurogenic niches resulted in impaired neurogenesis in healthy WT mice. This study therefore provides evidence that D2R blockade improves hippocampal and striatal deficits in HD mice although the underlying mechanism for this is unclear, and suggests that agents working within this network may have greater effects than previously thought.

Poster #S24 ABNORMAL STRESS RESPONSIVITY IN A RODENT DEVELOPMENTAL DISRUPTION MODEL OF SCHIZOPHRENIA

Huntington's disease (HD) is an inherited neurodegenerative disorder that is classically defined by a triad of movement and cognitive and psychiatric abnormalities with a well-established pathology that affects the dopaminergic systems of the brain. This has classically been described in terms of an early loss of dopamine D2 receptors (D2R), although interestingly the treatments most effectively used to treat patients with HD block these same receptors. We therefore sought to examine the dopaminergic system in HD not only in terms of striatal function but also at extrastriatal sites especially the hippocampus, given that transgenic (Tg) mice also exhibit deficits in hippocampal-dependent cognitive tests and a reduction in adult hippocampal neurogenesis. We showed that there was an early reduction of D2R in both the striatum and dentate gyrus (DG) of the hippocampus in the R6/1 transgenic HD mouse ahead of any overt motor signs and before striatal neuronal loss. Despite downregulation of D2Rs in these sites, further reduction of the dopaminergic input to these sites by either medial forebrain bundle lesions or receptor blockade using sulpiride was able to improve both deficits in motor performance and adult hippocampal neurogenesis. In contrast, a reduction in dopaminergic innervation of the neurogenic niches resulted in impaired neurogenesis in healthy WT mice. This study therefore provides evidence that D2R blockade improves hippocampal and striatal deficits in HD mice although the underlying mechanism for this is unclear, and suggests that agents working within this network may have greater effects than previously thought.

Habit learning and brain–machine interfaces (BMI): a tribute to Valentino Braitenberg’s “Vehicles”

Brain-Machine Interfaces (BMI) allow manipulation of external devices and computers directly with brain activity without involvement of overt motor actions. The neurophysiological principles of such robotic brain devices and BMIs follow Hebbian learning rules as described and realized by Valentino Braitenberg in his book "Vehicles," in the concept of a "thought pump" residing in subcortical basal ganglia structures. We describe here the application of BMIs for brain communication in totally locked-in patients and argue that the thought pump may extinguish-at least partially-in those people because of extinction of instrumentally learned cognitive responses and brain responses. We show that Pavlovian semantic conditioning may allow brain communication even in the completely paralyzed who does not show response-effect contingencies. Principles of skill learning and habit acquisition as formulated by Braitenberg are the building blocks of BMIs and neuroprostheses.