Steven L. Small

ACTION OBSERVATION HAS A POSITIVE IMPACT ON REHABILITATION OF MOTOR DEFICITS AFTER STROKE

Evidence exists that the observation of actions activates the same cortical motor areas that are involved in the performance of the observed actions. The neural substrate for this is the mirror neuron system. We harness this neuronal system and its ability to re-enact stored motor representations as a means for rehabilitating motor control. We combined observation of daily actions with concomitant physical training of the observed actions in a new neurorehabilitative program (action observation therapy). Eight stroke patients with moderate, chronic motor deficit of the upper limb as a consequence of medial artery infarction participated. A significant improvement of motor functions in the course of a 4-week treatment, as compared to the stable pre-treatment baseline, and compared with a control group have been found. The improvement lasted for at least 8 weeks after the end of the intervention. Additionally, the effects of action observation therapy on the reorganization of the motor system were investigated by functional magnetic resonance imaging (fMRI), using an independent sensorimotor task consisting of object manipulation. The direct comparison of neural activations between experimental and control groups after training with those elicited by the same task before training yielded a significant rise in activity in the bilateral ventral premotor cortex, bilateral superior temporal gyrus, the supplementary motor area (SMA) and the contralateral supramarginal gyrus. Our results provide pieces of evidence that action observation has a positive additional impact on recovery of motor functions after stroke by reactivation of motor areas, which contain the action observation/action execution matching system.

Escitalopram and Problem-Solving Therapy for Prevention of Poststroke Depression: A Randomized Controlled Trial

CONTEXT Depression occurs in more than half of patients who have experienced a stroke. Poststroke depression has been shown in numerous studies to be associated with both impaired recovery in activities of daily living and increased mortality. Prevention of depression thus represents a potentially important goal. OBJECTIVE To determine whether treatment with escitalopram or problem-solving therapy over the first year following acute stroke will decrease the number of depression cases that develop compared with placebo medication. DESIGN, SETTING, AND PARTICIPANTS A multisite randomized controlled trial for prevention of depression among 176 nondepressed patients was conducted within 3 months following acute stroke from July 9, 2003, to October 1, 2007. The 12-month trial included 3 groups: a double-blind placebo-controlled comparison of escitalopram (n = 59) with placebo (n = 58), and a nonblinded problem-solving therapy group (n = 59). MAIN OUTCOME MEASURES The main outcome measure was the development of major or minor poststroke depression based on symptoms elicited by the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) (DSM-IV) and the diagnostic criteria from DSM-IV for depression due to stroke with major depressive-like episode or minor depression (ie, research criteria). RESULTS Patients who received placebo were significantly more likely to develop depression than individuals who received escitalopram (11 major and 2 minor cases of depression [22.4%] vs 3 major and 2 minor cases of depression [8.5%], adjusted hazard ratio [HR], 4.5; 95% confidence interval [CI], 2.4-8.2; P < .001) and also more likely than individuals who received problem-solving therapy (5 major and 2 minor cases of depression [11.9%], adjusted HR, 2.2; 95% CI, 1.4-3.5; P < .001). These results were adjusted for history of mood disorders and remained significant after considering possible confounders such as age, sex, treatment site, and severity of impairment in the model. Using an intention-to-treat conservative method of analyzing the data, which assumed that all 27 patients who did not start randomized treatment would have developed depression, and controlling for prior history of mood disorders, escitalopram was superior to placebo (23.1% vs 34.5%; adjusted HR, 2.2; 95% CI, 1.2-3.9; P = .007), while problem-solving therapy was not significantly better than placebo (30.5% vs 34.5%; adjusted HR, 1.1; 95% CI, 0.8-1.5; P = .51). Adverse events, including all-cause hospitalizations, nausea, and adverse effects associated with escitalopram were not significantly different between the 3 groups. CONCLUSIONS In this study of nondepressed patients with recent stroke, the use of escitalopram or problem-solving therapy resulted in a significantly lower incidence of depression over 12 months of treatment compared with placebo, but problem-solving therapy did not achieve significant results over placebo using the intention-to-treat conservative method of analysis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00071643.

Listening to talking faces: motor cortical activation during speech perception

Neurophysiological research suggests that understanding the actions of others harnesses neural circuits that would be used to produce those actions directly. We used fMRI to examine brain areas active during language comprehension in which the speaker was seen and heard while talking (audiovisual) or heard but not seen (audio-alone) or when the speaker was seen talking with the audio track removed (video-alone). We found that audiovisual speech perception activated a network of brain regions that included cortical motor areas involved in planning and executing speech production and areas subserving proprioception related to speech production. These regions included the posterior part of the superior temporal gyrus and sulcus, the pars opercularis, premotor cortex, adjacent primary motor cortex, somatosensory cortex, and the cerebellum. Activity in premotor cortex and posterior superior temporal gyrus and sulcus was modulated by the amount of visually distinguishable phonemes in the stories. None of these regions was activated to the same extent in the audio- or video-alone conditions. These results suggest that integrating observed facial movements into the speech perception process involves a network of multimodal brain regions associated with speech production and that these areas contribute less to speech perception when only auditory signals are present. This distributed network could participate in recognition processing by interpreting visual information about mouth movements as phonetic information based on motor commands that could have generated those movements.

Functions of the mirror neuron system: implications for neurorehabilitation.

Mirror neurons discharge during the execution of hand object-directed actions and during the observation of the same actions performed by other individuals. These neurons were first identified in the ventral premotor cortex (area F5) and later on in the inferior parietal lobule of monkey brain, thus constituting the mirror neuron system. More recently, mirror neurons for mouth object-directed actions have also been found in the monkey. Several pieces of experimental data demonstrate that a mirror neuron system devoted to hand, mouth, and foot actions is also present in humans. In the present paper we review the experimental evidence on the role of the mirror neuron system in action understanding, imitation learning of novel complex actions, and internal rehearsal (motor imagery) of actions. On the basis of features of the mirror neuron system and its role in action understanding and imitation, we discuss the possible use of action observation and imitation as an approach for systematic training in the rehabilitation of patients with motor impairment of the upper limb after stroke.

The mind of expert motor performance is cool and focused

Extraordinary motor skills required for expert athletic or music performance require longstanding and intensive practice leading to two critical skills, a level of maximal performance that far exceeds that of non-experts and a degree of privileged focus on motor performance that excludes intrusions. This study of motor planning in expert golfers demonstrated their brain activation during their pre-shot routine to be radically different than in novices. The posterior cingulate, the amygdala-forebrain complex, and the basal ganglia were active only in novices, whereas experts had activation primarily in the superior parietal lobule, the dorsal lateral premotor area, and the occipital area. The fact that these differences are apparent before the golfer swings the club suggests that the disparity between the quality of the performance of novice and expert golfers lies at the level of the organization of neural networks during motor planning. In particular, we suggest that extensive practice over a long period of time leads experts to develop a focused and efficient organization of task-related neural networks, whereas novices have difficulty filtering out irrelevant information.

Lateralization of motor circuits and handedness during finger movements

Although functional lateralization in the human brain has been studied intensively, there remains significant controversy over the brain mechanisms that instantiate it. The main objective of the present study is to characterize the regions associated with the generation of different movements by the fingers of both hands by right‐ and left‐handed people. Thirteen right‐ and left‐handers were studied using blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) during performance of single and sequential finger movement tasks. We used single‐shot whole‐brain spiral fMRI to map the functional components of the motor system during these tasks. Regions of interest included the primary motor and sensory cortices, the pre‐motor cortices and the cerebellum.

Task-dependent organization of brain regions active during rest

The human brain demonstrates complex yet systematic patterns of neural activity at rest. We examined whether functional connectivity among those brain regions typically active during rest depends on ongoing and recent task demands and individual differences. We probed the temporal coordination among these regions during periods of language comprehension and during the rest periods that followed comprehension. Our findings show that the topography of this “rest network” varies with exogenous processing demands. The network encompassed more highly interconnected regions during rest than during listening, but also when listening to unsurprising vs. surprising information. Furthermore, connectivity patterns during rest varied as a function of recent listening experience. Individual variability in connectivity strength was associated with cognitive function: more attentive comprehenders demonstrated weaker connectivity during language comprehension, and a greater differentiation between connectivity during comprehension and rest. The regions we examined have generally been thought to form an invariant physiological and functional network whose activity reflects spontaneous cognitive processes. Our findings suggest that their function extends beyond the mediation of unconstrained thought, and that they play an important role in higher-level cognitive function.

Sports experience changes the neural processing of action language

Experience alters behavior by producing enduring changes in the neural processes that support performance. For example, performing a specific action improves the execution of that action via changes in associated sensory and motor neural circuitry, and experience using language improves language comprehension by altering the anatomy and physiology of perisylvian neocortical brain regions. Here we provide evidence that specialized (sports) motor experience enhances action-related language understanding by recruitment of left dorsal lateral premotor cortex, a region normally devoted to higher-level action selection and implementation—even when there is no intention to perform a real action. Experience playing and watching sports has enduring effects on language understanding by changing the neural networks that subserve comprehension to incorporate areas active in performing sports skills. Without such experience, sport novices recruit lower-level sensory-motor regions, thought to support the instantiation of movement, during language processing, and activity in primary motor areas does not help comprehension. Thus, the language system is sufficiently plastic and dynamic to encompass expertise-related neural recruitment outside core language networks.

The Interaction of Social and Emotional Processes in the Brain

Social stimuli function as emotional barometers for the immediate environment are the catalysts for many emotional reactions, and have inherent value for relationships and survival independent of their current emotional content. We, therefore, propose that the neural mechanisms underlying social and emotional information processing may be interconnected. In the current study, we examined the independent and interactive effects of social and emotional processes on brain activation. Whole-brain images were acquired while participants viewed and categorized affective pictures that varied on two dimensions: emotional content (i.e., neutral, emotional) and social content (i.e., faces/people, objects/scenes). Patterns of activation were consistent with past findings demonstrating that the amygdala and part of the visual cortex were more active to emotionally evocative pictures than to neutral pictures and that the superior temporal sulcus was more active to social than to nonsocial pictures. Furthermore, activation of the superior temporal sulcus and middle occipito-temporal cortex showed evidence of the interactive processing of emotional and social information, whereas activation of the amygdala showed evidence of additive effects. These results indicate that interactive effects occur early in the stream of processing, suggesting that social and emotional information garner greater attentional resources and that the conjunction of social and emotional cues results in synergistic early processing, whereas the amygdala appears to be primarily implicated in processing biologically or personally relevant stimuli, regardless of the nature of the relevance (i.e., social, emotional, or both).

Different Neural Circuits Subserve Reading before and after Therapy for Acquired Dyslexia

Rehabilitative measures for stroke are not generally based on basic neurobiological principles, despite evidence from animal models that certain anatomical and pharmacological changes correlate with recovery. In this report, we use functional magnetic resonance imaging (fMRI) to study in vivo human brain reorganization in a right handed patient with an acquired reading disorder from stroke. With phonological dyslexia, her whole-word (lexical) reading approach included inability to read nonwords and poor reading of function words. Following therapy, she was able to read nonwords and function words, and preferred a decompositional (sub-lexical) strategy in general. fMRI was performed during a reading task before and after treatment. Prior to therapy, her main focus of brain activation was in the left angular gyrus (area 39). After therapy, it was instead in the left lingual gyrus (area 18). This result suggests first that it is possible to alter brain physiology with therapy for acquired language disorders, and second, that two reading strategies commonly used in normal reading use distinct neural circuits, possibly reconciling several conflicting neuroimaging studies of reading.