Daniel J. Upton

Cortical inhibition in motor and non-motor regions: a combined TMS-EEG study.

A number of studies using paired pulse transcranial magnetic stimulation (TMS) have demonstrated that cortical inhibition (CI) of the motor cortex can be recorded and also gauged through surface electromyography. However, recording CI from other brain regions that are more directly related with the pathophysiology of some neurologic and psychiatric disorders (e.g., dorsolateral prefrontal cortex (DLPFC) in schizophrenia) was previously fraught with technical difficulties. This study was therefore designed to examine, through a combination of TMS with EEG, whether CI could be measured directly from the motor cortex, DLPFC, and another non-motor region. To index CI, long interval cortical inhibition (LICI; a TMS paradigm) was used in the motor cortex and DLPFC in 14 healthy subjects, and in the parietal lobe in 5 of those subjects. In the motor cortex, LICI resulted in a significant suppression in mean cortical evoked activity on EEG (37.31 ± 47.51 %). In the DLPFC, LICI resulted in a significant suppression (32.45 ± 47.86 %) in mean cortical evoked activity and did not correlate with LICI in the motor cortex although they did not significantly differ. In the parietal lobe, LICI resulted in significant suppression (47.76 ± 44.70 %) in mean cortical evoked activity. In conclusion, CI in the dorsolateral prefrontal cortex, motor cortex and parietal cortex were similar at 120% of motor threshold. These data suggest that CI can be recorded by combining TMS with EEG and may facilitate future research attempting to ascertain the role of CI in the pathophysiology of several neurologic and psychiatric disorders.

Chemoarchitecture of the middle temporal visual area in the marmoset monkey (Callithrix jacchus): laminar distribution of calcium-binding proteins (calbindin, parvalbumin) and nonphosphorylated neurofilament.

We studied the distributions of interneurons containing the calcium‐binding proteins parvalbumin and calbindin D‐28k, as well as that of pyramidal neurons containing nonphosphorylated neurofilament (NNF), in the middle temporal visual area (MT) of marmoset monkeys. The distributions of these classes of cells in MT are distinct from those found in adjacent areas. Similar to the primary visual area (V1), in MT, calbindin‐immunopositive neurons can be objectively classified into “dark” and “light” subtypes based on optical density of stained cell bodies. Calbindin‐positive dark neurons are particularly concentrated in layers 2 and 3, whereas light neurons have a more widespread distribution. In addition, a subcategory of calbindin‐positive dark neuron, characterized by a “halo” of stained processes surrounding the cell body, is found within and around layer 4 of MT and V1. These cells are rare in most other visual areas. In comparison, parvalbumin‐immunopositive cells in area MT have a relatively homogeneous distribution, although with a trend toward higher spatial density in lower layer 3, and are relatively uniform in terms of density of staining. Finally, MT shows a characteristic trilaminar distribution of NNF‐immunopositive pyramidal cells, with stained cell bodies evident in layers 3, 5, and 6. Although the laminar distribution of cells stained for the three markers overlap to some extent, these subcategories can be readily distinguished in terms of morphology, including cell body size. Chemoarchitectural parallels observed between MT and V1 suggest comparable physiological requirements and neuronal circuitry. J. Comp. Neurol. 500:832–849, 2007.

A comparative study of the effects of repetitive paired transcranial magnetic stimulation on motor cortical excitability

OBJECTIVES Various methods of application of repetitive transcranial magnetic stimulation (TMS) have been evaluated for their potential capacity to alter motor cortical excitability. Initial research suggests that the repetitive application of paired TMS pulses (repetitive paired pulse TMS (rppTMS)) may have greater effects on cortical excitability, perhaps through the facilitation of I-wave interaction. We aimed to compare the post-train effects of 15 min trains of rppTMS to investigate the potential therapeutic application of this technique as well as to compare it to a standard high frequency repetitive TMS paradigm. METHODS Ten normal subjects received three 15 min sessions of rppTMS, 5 Hz high frequency rTMS and sham TMS in randomised order. rppTMS consisted of a single train of 180 pulse pairs (0.2 Hz, 1.5 ms inter-stimulus interval, supra-threshold intensity) administered over 15 min. The rTMS condition involved 750 pulses provided in 5s 5 Hz trains with a 25s inter-train interval at 90% of the RMT. Motor evoked potential size and cortical silent period duration were assessed before and after each session. RESULTS There were no significant changes in cortical excitability produced by any of the stimulation conditions. Five hertz rTMS produced an increase in cortical silent period duration (p=0.004) which was not affected by rppTMS. CONCLUSIONS Fifteen minutes trains of 1.5ms rppTMS do not substantially increase post train cortical excitability. Repetitive brief trains of 5Hz rTMS also do not alter excitability but appear to effect cortical inhibition.

A study of intensity dependence of the auditory evoked potential (IDAEP) in medicated melancholic and non-melancholic depression

BACKGROUND Major Depressive Disorder is widely recognised to be a heterogeneous syndrome with numerous depressive phenotypes, one of which is melancholic depression. Patients with melancholic depression exhibit treatment responses and outcomes that differ from patients with non-melancholic depression. The current study aimed to assess whether differences existed between melancholic and non-melancholic subtypes of depression, as measured by the event related potential, intensity dependence of the auditory evoked potential (IDAEP). METHODS IDAEP was assessed in 14 melancholic and 13 non-melancholic depressed subjects and 14 controls. RESULTS The melancholic patients had a significantly shallower IDAEP slope than the non-melancholic patients not explained by depression severity or age. LIMITATIONS Antidepressants were taken by all patients in this study and the effect of continual use of these drugs on the IDAEP slopes has yet to be confirmed. CONCLUSIONS These results provide support for neurobiological differences between melancholic and non-melancholic depressive subtypes. Melancholic depression may be characterized by ongoing over function of the serotonin system in spite of medication treatment.

Effects of rTMS on an Auditory Oddball Task: a Pilot Study of Cortical Plasticity and the EEG

The objective of this study was to explore the effects of 1Hz repetitive transcranial magnetic stimulation (rTMS) applied to dorsal lateral prefrontal cortex (DLPFC) on both an EEG index of cortical excitation and inhibition, event-related desynchronization/synchronization (ERD/S) and on the P300 component of an auditory oddball-induced ERP. Eight normal participants received 15 minutes of 1Hz rTMS at 110% of the resting motor threshold to right DLPFC. ERD/S of alpha and beta bands was measured during an auditory oddball task immediately before and after stimulation. There was significantly less alpha desynchronization post-TMS, and this effect was widespread excepting posterior midline sites. No changes were found to oddball-P300 amplitudes or latencies. In conclusion, the findings of less alpha desynchronization post-TMS are compatible with notions of slow rTMS causing a decrease in cortical excitation.

An improved cognitive model of the Iowa and Soochow Gambling Tasks with regard to model fitting performance and tests of parameter consistency

The Iowa Gambling Task (IGT) and the Soochow Gambling Task (SGT) are two experience-based risky decision-making tasks for examining decision-making deficits in clinical populations. Several cognitive models, including the expectancy-valence learning (EVL) model and the prospect valence learning (PVL) model, have been developed to disentangle the motivational, cognitive, and response processes underlying the explicit choices in these tasks. The purpose of the current study was to develop an improved model that can fit empirical data better than the EVL and PVL models and, in addition, produce more consistent parameter estimates across the IGT and SGT. Twenty-six opiate users (mean age 34.23; SD 8.79) and 27 control participants (mean age 35; SD 10.44) completed both tasks. Eighteen cognitive models varying in evaluation, updating, and choice rules were fit to individual data and their performances were compared to that of a statistical baseline model to find a best fitting model. The results showed that the model combining the prospect utility function treating gains and losses separately, the decay-reinforcement updating rule, and the trial-independent choice rule performed the best in both tasks. Furthermore, the winning model produced more consistent individual parameter estimates across the two tasks than any of the other models.

Comparing the Iowa and Soochow Gambling Tasks in Opiate Users

The Iowa Gambling Task (IGT) is in many respects the gold standard for demonstrating decision making in drug using groups. However, it is not clear how basic task properties such as the frequency and magnitude of rewards and losses affect choice behavior in drug users and even in healthy players. In this study, we used a variant of the IGT, the Soochow Gambling Task (SGT), to observe choice behavior in opiate users and healthy decision makers in a task where reward frequency is not confounded with the long-term outcome of each alternative. In both opiate users (n = 26) and healthy controls (n = 27), we show that reward frequency strongly influences choice behavior in the IGT and SGT. Neither group showed a consistent preference across tasks for alternatives with good long-term outcomes, but rather, subjects appeared to prefer alternatives that win most frequently. We interpret this as evidence to suggest that healthy players perform better than opiate users on the IGT because they are able to utilize gain–loss frequencies to guide their choice behavior on the task. This challenges the previous notion that poorer performance on the IGT in drug users is due to an inability to be guided by future consequences.The Iowa Gambling Task (IGT) is in many respects the gold standard for demonstrating decision making in drug using groups. However, it is not clear how basic task properties such as the frequency and magnitude of rewards and losses affect choice behavior in drug users and even in healthy players. In this study, we used a variant of the IGT, the Soochow Gambling Task (SGT), to observe choice behavior in opiate users and healthy decision makers in a task where reward frequency is not confounded with the long-term outcome of each alternative. In both opiate users (n = 26) and healthy controls (n = 27), we show that reward frequency strongly influences choice behavior in the IGT and SGT. Neither group showed a consistent preference across tasks for alternatives with good long-term outcomes, but rather, subjects appeared to prefer alternatives that win most frequently. We interpret this as evidence to suggest that healthy players perform better than opiate users on the IGT because they are able to utilize gain-loss frequencies to guide their choice behavior on the task. This challenges the previous notion that poorer performance on the IGT in drug users is due to an inability to be guided by future consequences.

ERP correlates of response inhibition after-effects in the stop signal task.

Several studies have found that response inhibition in the stop signal task is associated with a delay in subsequent response speed, which may result from the automatic retrieval of a conflicting stimulus-goal association. This study investigated the neurophysiological correlates of this sequence effect using event related potentials (ERPs). ERPs were recorded in 17 healthy people while they performed the stop signal task. We found reduced P3b amplitude for responses following successful inhibition, but only when the stimulus was repeated from the previous trial (repetition-after-effects). For responses following failed inhibition, P3b amplitude was reduced regardless of stimulus repetition status. We also found a general increase in frontal N2 amplitude on response trials following inhibition, regardless of stimulus repetition or behavioural slowing. The complex pattern of ERP findings, dependent on stimulus repetition and success of inhibition, suggests multiple sources of behavioural slowing in the present data. ERP findings suggest that a memory retrieval processes underlies the repetition component of inhibition after effects. These findings are considered within the broader context of ERP findings in the negative priming literature.

A Combined rTMS and ERP Investigation of Dorsolateral Prefrontal Cortex Involvement in Response Inhibition

The stop signal task is used to investigate inhibition of an initiated response. Converging evidence suggests that right inferior prefrontal cortex is involved in this behavior, although other regions in the prefrontal cortex have also been implicated. One technique used to determine the contribution of specific cortical regions to behavior is repetitive transcranial magnetic stimulation (rTMS). In the present study, fourteen subjects performed the stop signal task before and after receiving a train of rTMS to the left and right dorsolateral prefrontal cortex (DLPFC). The effects of rTMS were determined using event-related potential (ERP) measures that have been associated with response inhibition in previous studies. Stimulation of left and right DLPFC did not affect ERP measures of response inhibition. This negative finding is interpreted with caution, but is consistent with a recent study which found that stimulation of the same region had no effect on a behavioral measure of response inhibition.

Stop task after-effects in schizophrenia: Behavioral control adjustments and repetition priming

Stop task after-effects are behavioral consequences of response inhibition (i.e., slowed response time), and may index both behavioral control adjustments and repetition priming. Patients with schizophrenia and healthy controls completed a stop task, and responses to the go signal were analyzed according to characteristics of the immediately preceding trial. Schizophrenia was associated with reduced slowing following unsuccessful response inhibition, however there was no evidence of impairments in repetition priming. These results support neurocognitive models of schizophrenia that suggest an absence or reduction of behavioral adjustments (perhaps reflecting impaired error detection), but are inconsistent with current retrieval-based repetition priming accounts.