Facilitation of probabilistic classification learning by transcranial direct current stimulation of the prefrontal cortex in the human

Abstract

The aim of our study was to test if the electrical stimulation of the prefrontal cortex (PFC) could modify probabilistic classification learning (PCL). Transcranial direct current stimulation (tDCS) was administered to the left prefrontal and to the primary visual cortex of 22 healthy subjects while they performed a PCL task. In this task subjects learned which of two outcomes would occur on each trial after presentation of a particular combination of cues. Ten minutes of anodal, but not cathodal, stimulation improved implicit learning only when the left PFC was stimulated. Our results show that implicit PLC can be modified by weak anodal tDCS, which probably increases neural excitability, as has been shown in the motor and visual cortices previously. Our results suggest that further studies on the facilitation of learning and memory processes by tDCS are warranted.

Introduction

The process of learning is thought to involve a network of connected areas of the brain. One of the most important and challenging problems in neuroscience is the identification of these areas, and their connections, and to improve learning and memory by external manipulations. Neurobehavioral studies on healthy human subjects, patients with different types of brain lesions, as well as animal studies, have distinguished between explicit or declarative and implicit or non-declarative memory (Reber, Knowlton, & Squire, 1996; Squire & Zola-Morgan, 1991, Tulving, 1983). Explicit memory pertains to a conscious recollection of previous experiences, with the subject’s awareness, at the time of the test, of a relation between the current experience and the original encoding. In contrast, implicit memory is the retrieval of stored information in the absence of any awareness that the current behaviour and experience have been influenced by a particular earlier happening (Schacter, 1992, Squire, 1994, Tulving, 2000). Implicit memory can be measured in different ways. Recently, the probabilistic classification learning (PCL) task has been introduced as a promising tool to investigate implicit learning functions (Knowlton et al., 1996, Knowlton et al., 1994; Reber et al., 1996). In this task, subjects are asked whether a specific combination of different geometric forms predicts rainy or sunny weather. Each combination is probabilistically related to a particular weather outcome, however the relationship is not absolute: in different percentages the combinations are associated with the opposite outcome. During the task individuals learn gradually which of two outcomes would occur in each trial given the particular combination of cues that appears, although they have no conscious knowledge of the rule.

Several studies suggest that intact neostriatal functions are necessary for this kind of implicit learning because subjects with basal ganglia disorders, such as Parkinson’s and Huntington’s disease and patients with Tourette syndrome had difficulties in PCL (Keri, Szlobodnyik, Benedek, Janka, & Gadoros, 2002; Knowlton et al., 1996, Reber et al., 1996). However, amnesic patients with damage to the medio-temporal or diencephalic areas showed a normal learning curve in the PCL task, although they were not able to define the meaning of cues explicitly (Knowlton et al., 1996). A recent fMRI study found that during a PCL task multiple brain regions of healthy subjects were activated, including bilateral frontal cortices, the occipital cortex (Oz) and the striatum (Poldrack, Prabhakaran, Seger, & Gabrieli, 1999).

Although the earlier mentioned patient studies imply that this kind of learning occurs in the neostriatum, it is possible that learning processes can be modified by the prefrontal cortex (PFC), since both brain areas are heavily interconnected. Alternatively, learning could occur in the PFC itself and thus modify neostriatal activation by the aforementioned prefrontal-striatal connections. Therefore, the aim of our study was to assess whether implicit PLC can be modified if the excitability level of PFC is modulated. To achieve this, we have up- or down-regulated the excitability of this area using a non-invasive stimulation technique, transcranial direct current stimulation (tDCS), the effectiveness of which has already been proven in motor and primary visual areas (Antal et al., 2001, Baudewig et al., 2001; Nitsche & Paulus, 2000, Nitsche & Paulus, 2001; Rosenkranz, Nitsche, Tergau, & Paulus, 2000). Weak cathodal stimulation, which probably causes membrane hyperpolarization, has been shown to decrease neuronal firing rates and diminish cerebral excitability while conversely anodal stimulation enhances it. The after-effects can be prolonged by increasing the current intensity or the duration of tDCS (Nitsche & Paulus, 2000, Nitsche & Paulus, 2001). Recently, it was found that anodal tDCS can modulate implicit motor learning in healthy human subjects while the primary motor cortex was stimulated (Nitsche et al., 2003). Here we show that anodal stimulation can improve PLC when the left PFC is stimulated.