Katsuyuki Sakai

Central mechanisms of motor skill learning

Recent studies have shown that frontoparietal cortices and interconnecting regions in the basal ganglia and the cerebellum are related to motor skill learning. We propose that motor skill learning occurs independently and in different coordinates in two sets of loop circuits: cortex-basal ganglia and cortex-cerebellum. This architecture accounts for the seemingly diverse features of motor learning.

Reading Hidden Intentions in the Human Brain

When humans are engaged in goal-related processing, activity in prefrontal cortex is increased. However, it has remained unclear whether this prefrontal activity encodes a subjects current intention. Instead, increased levels of activity could reflect preparation of motor responses, holding in mind a set of potential choices, tracking the memory of previous responses, or general processes related to establishing a new task set. Here we study subjects who freely decided which of two tasks to perform and covertly held onto an intention during a variable delay. Only after this delay did they perform the chosen task and indicate which task they had prepared. We demonstrate that during the delay, it is possible to decode from activity in medial and lateral regions of prefrontal cortex which of two tasks the subjects were covertly intending to perform. This suggests that covert goals can be represented by distributed patterns of activity in the prefrontal cortex, thereby providing a potential neural substrate for prospective memory. During task execution, most information could be decoded from a more posterior region of prefrontal cortex, suggesting that different brain regions encode goals during task preparation and task execution. Decoding of intentions was most robust from the medial prefrontal cortex, which is consistent with a specific role of this region when subjects reflect on their own mental states.

Paired-pulse magnetic stimulation of the human motor cortex: differences among I waves.

1 In paired‐pulse cortical stimulation experiments, conditioning subthreshold stimuli suppress the electromyographic (EMG) responses of relaxed muscles to suprathreshold magnetic test stimuli at short interstimulus intervals (ISIs) (1‐5 ms) and facilitate them at long ISIs (8‐15 ms). 2 We made paired‐pulse magnetic stimulation studies on the response of the first dorsal interosseous muscle (FDI) produced by I1 or I3 waves using our previously reported method which preferentially elicits one group of I waves when subjects make a slight voluntary contraction. In some experiments the conditioning and test stimuli were oppositely directed, in the others they were oriented in the same direction. Single motor unit responses were recorded with a concentric needle electrode, and surface EMG responses with cup electrodes. 3 In post‐stimulus time histograms (PSTHs) of the firing probability of motor units, the peaks produced by I3 waves were decreased by a subthreshold conditioning stimulus that preferentially elicited I1 or I3 waves at an ISI of 4 ms. The amount of decrement depended on the intensity of the conditioning stimulus. The stronger the conditioning stimulus, the greater the suppression. In contrast, the peaks produced by I1 waves were little affected by any type of subthreshold conditioning stimulus, given 4 ms prior to the test stimulus. At an ISI of 10 ms, a subthreshold conditioning stimulus slightly decreased the size of the peak produced by the I3 waves, but did not affect the peaks evoked by I1 waves. 4 Surface EMGs showed that a subthreshold conditioning stimulus suppressed the responses produced by I3 waves irrespective of its current direction (anterior or posterior). Both the amount and duration of suppression depended on the intensity of the conditioning stimulus, but not on its current direction. Both parameters increased when the intensity increased. At a high intensity conditioning stimulus, suppression was evoked at ISIs of 1‐20 ms, compatible with the duration of GABA‐mediated inhibition found in animal experiments. Responses produced by I1 waves were little affected by any type of subthreshold conditioning stimulus. 5 We conclude that a subthreshold conditioning stimulus given over the motor cortex moderately suppresses I3 waves but does not affect I1 waves. The duration of suppression of the I3 waves supports the idea that this is an effect of GABAergic inhibition within the motor cortex.

Task Set and Prefrontal Cortex

A task set is a configuration of cognitive processes that is actively maintained for subsequent task performance. Single-unit and brain-imaging studies have identified the neural correlates for task sets in the prefrontal cortex. Here I examine whether the neural data obtained thus far are sufficient to explain the behaviors that have been illustrated within the conceptual framework of task sets. I first discuss the selectivity of neural activity in representing a specific task. I then discuss the competitions between neural representations of task sets during task switch. Finally I discuss how, in neural terms, a task set is implemented to facilitate task performance. The processes of representing, updating, and implementing task sets occur in parallel at multiple levels of brain organization. Neural accounts of task sets demonstrate that the brain determines our thoughts and behaviors.

Chunking during human visuomotor sequence learning

Motor sequence learning is a process whereby a series of elementary movements is re-coded into an efficient representation for the entire sequence. Here we show that human subjects learn a visuomotor sequence by spontaneously chunking the elementary movements, while each chunk acts as a single memory unit. The subjects learned to press a sequence of 10 sets of two buttons through trial and error. By examining the temporal patterns with which subjects performed a visuomotor sequence, we found that the subjects performed the 10 sets as several clusters of sets, which were separated by long time gaps. While the overall performance time decreased by repeating the same sequence, the clusters became clearer and more consistent. The cluster pattern was uncorrelated with the distance of hand movements and was different across subjects who learned the same sequence. We then split a learned sequence into three segments, while preserving or destroying the clusters in the learned sequence, and shuffled the segments. The performance on the shuffled sequence was more accurate and quicker when the clusters in the original sequence were preserved than when they were destroyed. The results suggest that each cluster is processed as a single memory unit, a chunk, and is necessary for efficient sequence processing. A learned visuomotor sequence is hierarchically represented as chunks that contain several elementary movements. We also found that the temporal patterns of sequence performance transferred from the nondominant to dominant hand, but not vice versa. This may suggest a role of the dominant hemisphere in storage of learned chunks. Together with our previous unit-recording and imaging studies that used the same learning paradigm, we predict specific roles of the dominant parietal area, basal ganglia, and presupplementary motor area in the chunking.

Prefrontal Set Activity Predicts Rule-Specific Neural Processing during Subsequent Cognitive Performance

Prefrontal neurons have been shown to represent task rules. Here we show the mechanisms by which the rule-selective activity in the prefrontal cortex influences subsequent cognitive performance based on that rule. Using functional magnetic resonance imaging, we found that the frontopolar cortex interacted with posterior areas differently depending on whether subjects were going to perform a phonological or semantic task. Moreover, we found that the sustained “set” activity in this region predicted the activity that could be recorded in the posterior areas during the performance, as well as the speed of that performance. We argue that the prefrontal set activity does not reflect simple maintenance of the task rules but the process of implementing the rule for subsequent cognitive performance and that this is done through rule-selective interactions with areas involved in execution of the tasks.

Task-specific signal transmission from prefrontal cortex in visual selective attention

Our voluntary behaviors are thought to be controlled by top-down signals from the prefrontal cortex that modulate neural processing in the posterior cortices according to the behavioral goal. However, we have insufficient evidence for the causal effect of the top-down signals. We applied a single-pulse transcranial magnetic stimulation over the human prefrontal cortex and measured the strength of the top-down signals as an increase in the efficiency of neural impulse transmission. The impulse induced by the stimulation transmitted to different posterior visual areas depending on the domain of visual features to which subjects attended. We also found that the amount of impulse transmission was associated with the level of attentional preparation and the performance of visual selective-attention tasks, consistent with the causal role of prefrontal top-down signals.

Shortening of simple reaction time by peripheral electrical and submotor-threshold magnetic cortical stimulation

Abstract Subthreshold transcranial magnetic stimulation (TMS) over the motor cortex can shorten the simple reaction time in contralateral arm muscles if the cortical shock is given at about the same time as the reaction stimulus. The present experiments were designed to investigate whether this phenomenon is due to a specific facilitatory effect on cortical circuitry. The simple visual reaction time was shortened by 20–50 ms when subthreshold TMS was given over the contralateral motor cortex. Reaction time was reduced to the same level whether the magnetic stimulus was given over the bilateral motor cortices or over other points on the scalp (Cz, Pz). Indeed, similar effects could be seen with conventional electrical stimulation over the neck, or even when the coil was discharged (giving a click sound) near the head. We conclude that much of the effect of TMS on simple reaction time is due to intersensory facilitation, although part of it may be ascribed to a specific effect on the excitability of motor cortex.

Facilitatory effect of tonic voluntary contraction on responses to motor cortex stimulation

To investigate the mechanisms underlying the facilitation of responses to motor cortical stimulation produced by tonic voluntary contraction, we studied the facilitatory effects in 7 normal volunteers during different levels of muscle contraction. Responses were similarly facilitated by voluntary contraction with 3 forms of stimulation: magnetic cortical, electrical cortical, and foramen magnum level stimulation. At a high level of contraction, however, only magnetic responses were markedly facilitated. We conclude that the facilitation of responses to cortical stimulation induced by tonic voluntary contraction occurs mainly at the spinal level, but that cortical excitability changes also contribute to the enlargement of magnetic responses in the case of a high level of contraction.

Neural Circuitry Underlying Rule Use in Humans and Nonhuman Primates

Much of our behavior is focused on minimizing or maximizing a particular goal state. For example, animals generally seek to maximize food intake and minimize energy expenditure ([Stephens and Krebs, 1986][1]), although some humans strive to achieve the exact opposite goals. Instrumental to goal-