R. Chris Miall

Remembering the time: a continuous clock

The neural mechanisms for time measurement are currently a subject of much debate. This article argues that our brains can measure time using the same dorsolateral prefrontal cells that are known to be involved in working memory. Evidence for this is: (1) the dorsolateral prefrontal cortex is integral to both cognitive timing and working memory; (2) both behavioural processes are modulated by dopamine and disrupted by manipulation of dopaminergic projections to the dorsolateral prefrontal cortex; (3) the neurons in question ramp their activity in a temporally predictable way during both types of processing; and (4) this ramping activity is modulated by dopamine. The dual involvement of these prefrontal neurons in working memory and cognitive timing supports a view of the prefrontal cortex as a multipurpose processor recruited by a wide variety of tasks.

Disruption of State Estimation in the Human Lateral Cerebellum

The cerebellum has been proposed to be a crucial component in the state estimation process that combines information from motor efferent and sensory afferent signals to produce a representation of the current state of the motor system. Such a state estimate of the moving human arm would be expected to be used when the arm is rapidly and skillfully reaching to a target. We now report the effects of transcranial magnetic stimulation (TMS) over the ipsilateral cerebellum as healthy humans were made to interrupt a slow voluntary movement to rapidly reach towards a visually defined target. Errors in the initial direction and in the final finger position of this reach-to-target movement were significantly higher for cerebellar stimulation than they were in control conditions. The average directional errors in the cerebellar TMS condition were consistent with the reaching movements being planned and initiated from an estimated hand position that was 138 ms out of date. We suggest that these results demonstrate that the cerebellum is responsible for estimating the hand position over this time interval and that TMS disrupts this state estimate.

Effects of agency on movement interference during observation of a moving dot stimulus.

Human movement performance is subject to interference if the performer simultaneously observes an incongruent action. It has been proposed that this phenomenon is due to motor contagion during simultaneous movement performance–observation, with coactivation of shared action performance and action observation circuitry in the premotor cortex. The present experiments compared the interference effect during observation of a moving person with observation of moving dot stimuli: The dot display followed either a biologically plausible or implausible velocity profile. Interference effects due to dot observation were present for both biological and nonbiological velocity profiles when the participants were informed that they were observing prerecorded human movement and were absent when the dot motion was described as computer generated. These results suggest that the observers belief regarding the origin of the dot motion (human–computer generated) modulates the processing of the dot movement stimuli on their later integration within the motor system, such that the belief regarding their biological origin is a more important determinant of interference effects than the stimulus kinematics.

Disruption of the dorsolateral prefrontal cortex facilitates the consolidation of procedural skills

In explicit sequence learning tasks, an improvement in performance (skill) typically occurs after sleep—leading to the recent literature on sleep-dependent motor consolidation. Consolidation can also be facilitated during wakefulness if declarative knowledge for the sequence is reduced through a secondary cognitive task. Accordingly, declarative and procedural consolidation processes appear to mutually interact. Here we used TMS to test the hypothesis that functions in the dorsolateral prefrontal cortex (DLPFC) that support declarative memory formation indirectly reduce the formation of procedural representations. We hypothesize that disrupting the DLPFC immediately after sequence learning would degrade the retention or the consolidation of the sequence within the declarative memory system and thus facilitate consolidation within procedural memory systems, evident as wakeful off-line skill improvement. Inhibitory theta-burst TMS was applied to the left DLPFC (n = 10), to the right DLPFC (n = 10), or to an occipital cortical control site (n = 10) immediately after training on the serial reaction time task (SRTT). All groups were retested after eight daytime hours without sleep. TMS of either left or right DLPFC lead to skill improvements on the SRTT. Increase in skill was greater following right DLPFC stimulation than left DLPFC stimulation; there was no improvement in skill for the control group. Across all participants, free recall of the sequence was inversely related to the improvements in performance on the SRTT. These results support the hypothesis of interference between declarative and procedural consolidation processes and are discussed in the framework of the interactions between memory systems.

Inter-individual variability in optimal current direction for transcranial magnetic stimulation of the motor cortex

We evaluated inter-individual variability in optimal current direction for biphasic transcranial magnetic stimulation (TMS) of the motor cortex. Motor threshold for first dorsal interosseus was detected visually at eight coil orientations in 45 degrees increments. Each participant (n=13) completed two experimental sessions. One participant with low test-retest correlation (Pearsons r<0.5) was excluded. In four subjects, visual detection of motor threshold was compared to EMG detection; motor thresholds were very similar and highly correlated (0.94-0.99). Similar with previous studies, stimulation in the majority of participants was most effective when the first current pulse flowed towards postero-lateral in the brain. However, in four participants, the optimal coil orientation deviated from this pattern. A principal component analysis using all eight orientations suggests that in our sample the optimal orientation of current direction was normally distributed around the postero-lateral orientation with a range of 63 degrees (S.D.=13.70 degrees). Whenever the intensity of stimulation at the target site is calculated as a percentage from the motor threshold, in order to minimize intensity and side-effects it may be worthwhile to check whether rotating the coil 45 degrees from the traditional posterior-lateral orientation decreases motor threshold.

Cerebellar Transcranial Direct Current Stimulation (ctDCS) A Novel Approach to Understanding Cerebellar Function in Health and Disease

The cerebellum is critical for both motor and cognitive control. Dysfunction of the cerebellum is a component of multiple neurological disorders. In recent years, interventions have been developed that aim to excite or inhibit the activity and function of the human cerebellum. Transcranial direct current stimulation of the cerebellum (ctDCS) promises to be a powerful tool for the modulation of cerebellar excitability. This technique has gained popularity in recent years as it can be used to investigate human cerebellar function, is easily delivered, is well tolerated, and has not shown serious adverse effects. Importantly, the ability of ctDCS to modify behavior makes it an interesting approach with a potential therapeutic role for neurological patients. Through both electrical and non-electrical effects (vascular, metabolic) ctDCS is thought to modify the activity of the cerebellum and alter the output from cerebellar nuclei. Physiological studies have shown a polarity-specific effect on the modulation of cerebellar–motor cortex connectivity, likely via cerebellar–thalamocortical pathways. Modeling studies that have assessed commonly used electrode montages have shown that the ctDCS-generated electric field reaches the human cerebellum with little diffusion to neighboring structures. The posterior and inferior parts of the cerebellum (i.e., lobules VI-VIII) seem particularly susceptible to modulation by ctDCS. Numerous studies have shown to date that ctDCS can modulate motor learning, and affect cognitive and emotional processes. Importantly, this intervention has a good safety profile; similar to when applied over cerebral areas. Thus, investigations have begun exploring ctDCS as a viable intervention for patients with neurological conditions.

Functional Imaging: Is the Resting Brain Resting?

It is often assumed that the human brain only becomes active to support overt behaviour. A new study challenges this concept by showing that multiple neural circuits are engaged even at rest. We highlight two complementary hypotheses which seek to explain the function of this resting activity.

Behavioural aspects of cerebellar function in adults with Asperger syndrome

Aside from social deficits, Asperger and autistic individuals also exhibit motor control abnormalities such as impaired gait, balance, manual dexterity and grip. One brain area that has consistently been reported on autopsy and imaging studies to be abnormal in such individuals is the cerebellum. As the cerebellum controls sensorimotor coordination and lesions here typically cause hypotonia, dysmetria and dyscoordination, we performed a series of quantitative tests aimed at investigating cerebellar function in Asperger individuals. Tests examining visually guided movement (rapid pointing), speeded complex movement (finger tapping, rapid hand turning), muscle tone (catching dropped weight), prediction, coordination and timing (balance, grip force and interval timing) were conducted on 12 Asperger subjects and 12 age and IQ matched controls. In comparison to control subjects, Asperger subject’s demonstrated: (i) decreased pointing accuracy and rate, (ii) increased postural instability, and (iii) decreased timing accuracy. IQ was found to co-vary with some parameters of each of these tasks and no further impairments were found on the remaining tests. We suggest that these specific deficits reflect impairment in the ability to integrate sensory input with appropriate motor commands and are consistent with cerebellar dysfunction in Asperger syndrome.

Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex

Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field.

Force related activations in rhythmic sequence production

Brain imaging studies have implicated the basal ganglia in the scaling of movement velocity. Basal ganglia activation has also been reported for movement timing. We investigated the neural correlates of scaling of force and time in the production of rhythmic motor sequences using functional magnetic resonance imaging (fMRI) of the human brain. Participants (N = 13) were imaged while squeezing a rigid force transducer in a near isometric manner between thumb and index finger, to reproduce four different rhythmic sequences. The responses were separated by either equal (600 ms) or alternating (400, 800 ms) intervals, and produced with either equal (12 N) or alternating (8, 16 N) forces pulses. Intervals and force levels were balanced across each condition. The primary motor cortex (M1), supplementary motor area (SMA), basal ganglia, thalamus, and cerebellum were activated during the production of sequences marked by equal interval and force. There was no reliable main effect of alternating interval. In contrast, greater activation of these regions was associated with the extra demands of responding with alternating force pulses. We interpret the data as identifying a significant role of the BG in the control of force. In addition, the results indicate the importance of monitoring force when studying brain activation associated with motor timing.