Marjan Jahanshahi

The Role of the Dorsolateral Prefrontal Cortex in Random Number Generation: A Study with Positron Emission Tomography

Random number generation (RNG) engages a number of executive processes. We used positron emission tomography (PET) to measure regional cerebral blood flow (rCBF) in six volunteers who performed RNG and a control counting (COUNT) task at six rates paced by a tone. This provided a systematic variation of difficulty of RNG. Relative to COUNT, RNG was associated with significant activation of the left dorsolateral prefrontal cortex (DLPFC), the anterior cingulate, the superior parietal cortex bilaterally, the right inferior frontal cortex, and the left and right cerebellar hemispheres. Faster rates of RNG were associated with a significant decrease in regional cerebral blood flow (rCBF) in the left and right DLPFC and the right superior parietal cortex. rCBF in the left DLPFC was significantly and negatively associated with count score 1, a measure of habitual counting during RNG. These results are discussed in relation to the network modulation model of RNG developed on the basis of our previous studies using transcranial magnetic stimulation and dual task paradigms. This suggests that during RNG, suppression of habitual counting is achieved through the modulatory (inhibitory) influence of the left DLPFC over a number associative network distributed in the superior temporal cortex. At faster rates of RNG the synchronization demands of paced RNG result in the breakdown of this modulatory influence, which is evident from decreased rCBF in the left DLPFC and increased habitual counting at faster rates.

Willed action and its impairments.

Actions are goal-directed behaviours that usually involve movem ent. There is evidence that intentional self-generated actions (willed actions) are controlled differently from routine, stereotyped actions that are externally triggered by environmental stimuli. We review evidence from investigations using positron emission tomography (PET), recordings of movement-related cortical potentials (MRCPs) or transcranial magnetic stimulation (TMS), and conclude that willed actions are controlled by a network of frontal cortical (dorsolateral prefrontal cortex, supplementary motor area, anterior cingulate) and subcortical (thalamus and basal ganglia) areas. We also consider evidence suggesting that some of the cognitive and motor deficits of patients with frontal lesions, Parkinsons disease, or schizophrenia as well as apathy and abulia and rarer phenomena such as primary obsessional slowness can be considered as reflecting im pairment of willed actions. We propose that the concept of a willed action system based on the frontostriatal circuits provides a useful framework for integrating the cognitive, motor, and motivational deficits found in these disorders. Problems remaining to be resolved include: identification of the component processes of willed actions; the specific and differential role played by each of the frontal cortical and subcortical areas in the control of willed actions; the specific mechanisms of impairm ent of willed actions in Parkinsons disease, schizophrenia, and frontal damage; and the precise role of the neurotransmitter dopamine in the willed action system.

Executive processes in Parkinson's - Disease random number generation and response suppression

In producing random numbers, subjects typically deviate systematically from statistical randomness. It is considered that these biases reflect constraints imposed by underlying structures and processes, rather than a deficient concept of randomness. Random number generation (RNG) places considerable demands on executive processes, and provides a possibly useful tool for their investigation. A group of patients with Parkinsons disease (PD) and a group of controls were tested on a RNG task, both alone and with a concurrent attention-demanding task (manual tracking). Both groups showed the biases in RNG described previously, including a strong counting tendency and repetition avoidance. Overall RNG performance did not differ between the groups, although differences were found in the counting biases in the patient and control groups, with the controls showing a bias towards counting in twos, and the patients a bias towards counting in ones. The secondary task reversed the bias shown by controls and exacerbated the bias in the patients. A network modulation model may help explain many of the features of RNG. We suggest that naturally biased output from an associative network must be actively suppressed by an attention-demanding, limited-capacity process. This suppression may be disrupted by the pathophysiology of PD and by concurrent tasks. Convergent evidence from various sources is discussed which supports a role of the dorsolateral prefrontal cortex (DLPFC) in this process.

The left dorsolateral prefrontal cortex and random generation of responses: studies with transcranial magnetic stimulation

Evidence from PET studies suggests that the dorsolateral prefrontal cortex (DLPFC) is involved in generation of random responses. We used TMS to examine the specific role of this area in random generation of responses, a task which requires holding information on line, suppression of habitual or stereotyped response patterns, intrinsic response generation, monitoring of responses and modification of production strategies. From the results of a previous study of the effects of TMS on random number generation, we proposed a network modulation model, whereby suppression of habitual responses is considered a key process of random response generation and is achieved through the modulatory influence of the left DLPFC over an associative network distributed in the superior temporal cortex. The aim of the present study was to further investigate the generality of this model by examining the effects of short trains of TMS over the left or right DLPFC or medial frontal cortex on random letter generation in healthy participants. TMS over the left DLPFC significantly increased non-randomness relative to control no stimulation trials, which was not obtained with TMS over the right DLPFC or medial frontal cortex. The results suggest the generality of network modulation model of random response generation.

Uncoupling of contingent negative variation and alpha band event-related desynchronization in a go/no-go task

OBJECTIVESnTo examine how the differences in the sequences of brain activation during the go/no-go delayed response choice reaction time (RT) task are reflected into two concurrent methods of measuring brain electrical activity, the alpha band event-related desynchronization (alpha ERD) and the contingent negative variation (CNV).nnnMETHODSnalpha ERD and CNV were calculated using appropriate techniques from the same samples of electroencephalographic activity recorded during performance of a cued choice go/no-go delayed response RT task (i.e. S1 (go/no-go)--S2 paradigm) in 8 healthy subjects.nnnRESULTSnAll segments of the CNV traces were different in the go and the no-go conditions. The go CNV traces displayed a typical pattern of slow rising negativity reflecting the build-up of attentional resources necessary for adequate performance of the task. On the other hand, the no-go traces remained close to zero reflecting the withdrawal of further preparation after evaluation of S1. During the same period, both go and no-go ERD traces showed a gradual decrease in alpha band power (desynchronization) that was evident until shortly before the presentation of S2. It was only in the 500 ms before S2 presentation that there was any indication that the go and no-go ERD traces were different, but this did not reach statistical significance.nnnCONCLUSIONSnOur data show that the pattern of the go/no-go difference in alpha ERD traces does not correspond to the pattern that can be seen in the CNV traces. This suggests that there is no direct coupling of CNV and alpha ERD, most probably because they measure different aspects of cortical electrical activity. In addition, the extent of the no-go alpha ERD reveals that refraining from performance of a pre-programmed movement is by no means a passive/inactive process.

Executive dysfunction in Parkinson's disease is associated with altered pallidal–frontal processing

Executive dysfunction in Parkinsons disease is well documented, but it is still unclear whether this results from (i) prefrontal dysfunction, (ii) striatal dysfunction, or (iii) altered striatal outflow to the prefrontal cortex. To clarify this issue, we used H(2)(15)O PET to asses six nondemented and nondepressed patients with Parkinsons disease and six matched controls while they performed a task involving executive function, random number generation (RNG), and a control counting task. To assess the effect of increasing task demands, each task was performed at three rates. Both groups showed significant increase in nonrandomness of responses during RNG at faster rates, which was differentially greater for the patients at the faster rate. The controls showed significant activation of the lateral and medial prefrontal cortex and superior and medial parietal cortex during RNG relative to counting. For the same comparison, the patients did not show any activity in medial frontal structures. The controls showed significantly greater mesial frontotemporal activation during counting than RNG, whereas the patients did not show any modulation of regional cerebral blood flow (rCBF) in these areas with task. With faster rates of RNG, the controls showed rCBF increase in the right internal segment of globus pallidus (GPi) and a decrease in frontal cortex. The patients showed the opposite pattern of subcortical and frontal rCBF change with faster rates. The results suggest that executive dysfunction in Parkinsons disease is associated with a failure to modulate frontal activation with increased task demands (nature of task or rate), a deficit associated with altered rCBF in the GPi, the final basal ganglia output pathway to frontal cortex rather than any intrinsic prefrontal dysfunction.

Rapid rate transcranial magnetic stimulation – a safety study

We assessed the safety of repeated short trains (4 stimuli) of rapid-rate transcranial magnetic stimulation (rrTMS) over the left motor cortex in 6 healthy normal subjects. rrTMS involved two separate blocks of 50 consecutive trains of 4 stimuli at a frequency of 20 Hz and an intensity of 5-10% above active motor threshold. We monitored EEG, and assessed aspects of neurological (balance, gait, two-point discrimination, blood pressure, pulse rate), cognitive (attention, memory, executive function) and motor function (speed of movement initiation and execution and manual dexterity) before and after the two blocks of rrTMS. EMG was also recorded from a number of hand, forearm and arm muscles contralateral to the site of stimulation. Two blocks of repeated rrTMS at 20 Hz and 5-10% above active motor threshold did not produce any adverse effects. Measures of neurological, cognitive and motor function showed no change following rrTMS. From the EMG recording there was evidence of increase in the amplitude of the motor evoked potentials (MEPs) recorded from the biceps in one subject during the first block of rrTMS, but this did not occur in the second block. A similar magnification of MEPs was also observed in another subject only during the second block of stimulation. When applied using parameters falling within published guidelines (Pascual-Leone et al., 1993; Pascual-Leone et al., 1994), repeated rrTMS is a relatively safe technique in healthy normal subjects. As rrTMS allows disruption of cortical function for a longer period, it has the potential of becoming a particularly useful tool for the study of cognitive function as well as sensory or motor function.

Cortical potentials related to the nogo decision.

Abstract. The go/nogo reaction time task has been frequently used to assess volitional inhibition. Psychophysiological studies of the correlates of the go/nogo decision have almost exclusively been concerned with N2 and P3 potentials of the event-related potentials (ERPs). However, in studies where the EMG onset latency was available, it was obvious that this latency was shorter than or at least equal to the latencies of the studied cerebral potentials. In this study, by concurrent recording of the EEG and EMG activity we aimed to better define the temporal relationship between cortical activity and motor response. Particularly, we wanted to identify the early (i.e. pre EMG-onset) electrophysiological correlates of the nogo decision. We used a modified S1-S2 paradigm that involved a two-stage go/nogo decision. In this task both S1 and S2 were informative and required the subject to make a decision, but the nature of the decision differed. The decision at S1 involved whether to prepare a movement, whereas the decision at S2 involved whether to initiate or inhibit an already prepared response. To better visualise the nogo decision related components of the ERPs, the go ERPs were subtracted from the corresponding nogo ERPs and difference ERPs were formed. Before EMG onset, a small negative component common to both go/nogo difference traces and corresponding roughly with the N1 wave was detected. It is suggested that this early negativity may be a more specific electrophysiological reflection of the nogo decision proper.

The mode of movement selection - Movement-related cortical potentials prior to freely selected and repetitive movements

Abstractu2002In two previous studies, the readiness potential (RP) has been reported to be influenced by the mode of movement selection. Freely selected movements were found to have a higher RP amplitude than fixed repetitive movements. This was attributed to the higher demands on planning for the performance of freely selected movements. However, movements in the free mode are distinct from movements in the fixed mode in more than one respect. For example, they are also associated with a higher degree of alteration of the side and/or the finger of movement execution and hence serial “novelty” across blocks of trials. The aim of our study was to establish whether the greater novelty of movements in the free mode could also contribute to the enhanced RP amplitude of movements in the free mode of movement selection by comparing free versus fixed movements performed in long and short sequences that differ in terms of serial novelty. The RP was recorded in 31 healthy young subjects with electrodes placed over Fz, C3, Cz, C4 and Pz. Two types of movement were studied: randomly chosen button presses with right or left index or middle finger (free mode), and repetitive pressing of a predetermined button (fixed mode). We found that: (1) in confirmation of previous studies, the amplitude of the RP was higher for freely selected than free movements; (2) the effect of the mode of movement selection was present over central electrodes but was most pronounced for parietal electrode Pz, with movements in the free mode showing the earliest and greatest increase in negativity at this site; (3) this parietally enhanced negativity in free compared with the fixed mode was absent after the subjects had performed a block of long movement sequences, suggesting that serial novelty of movements also contributed to the effect of mode on the RP amplitude; (4) both the latency and the magnitude of the lateralized readiness potential (LRP) were altered by the mode of movement selection. Movements in the free mode showed an earlier onset of the LRP, which had a higher peak than the LRP prior to movements in the fixed mode. This effect was mainly due to an increased amplitude of the RP over the electrode contralateral to the side of movement prior to freely selected movements. These findings are discussed in relation to previous RP and positron emission tomography studies.

Cognitive-Motor Dysfunction in Parkinson’s Disease

Patients with Parkinsons disease (PD) present with a wide range of cognitive and motor dysfunctions. Attempts to fit these deficits into a neuroanatomical framework have tended to emphasise their separateness. This paper, however, takes a broader perspective based on the concept of action-purposeful goal-directed behaviour-which serves to integrate the various deficits into a common framework. Of the motor symptoms of PD, akinesia is chosen as representing a breakdown in a distributed system of action control. Three aspects of akinesia are considered-slowness to initiate movement, slowness to execute movement and poverty of spontaneous movement. All are seen as being surface manifestation of the systems attempts to cope with or adapt to the limitations imposed by the disease process, at a cognitive, motor and integrative level.